CNS Effects of Aldosterone :
|
|
- Jayson Joshua Cook
- 5 years ago
- Views:
Transcription
1 CNS Effects of Aldosterone : Critical Roles in salt-sensitive sensitive hypertension and CHF. Frans HH Leenen MD, PhD, FRCPC, FAHA
2 2 Renin Angiotensin Aldosterone System Circulatory RAAS Tissue RAAS: - arteries, heart - kidneys - brain
3 3 Aldosterone, Ang II and the CNS Source: Function: circulation or locally produced? irrespective of source Salt Sensitive hypertension : circulatory RAAS brain RAAS CHF post MI : circulatory & cardiac RAAS brain RAAS
4 4 Salt and Circulatory RAAS in Dahl R and S rats. 1 Plasma Aldosterone 2 Plasma Ang II pg/ /ml pg/m ml R S R S Reg Salt High Salt for 4 weeks
5 5 Salt and tissue RAAS in Dahl S Angiotensin II Aldosterone Control 8% for 3 wks (Bayorh et al. Clin Exper Hypertens 25)
6 Salt and hypothalamic aldosterone and corticosterone in Dahl S 6 Aldosterone 5 12 Corticosterone pg/g 2 ng/g p<.5 vs RNa RNa HNa
7 CSF [Na + ] & MAP on high salt in Dahl S versus R CS SF Na + (mo ol/l) Plasma [Na + ] M AP (mmhg g) Dahl S Dahl R mmo ol/l RNa HNa 9 8 p<.5 vs RNa Days D D N D N D N D N D N D N High salt (Huang et al. Am J Physiol 24)
8 pg/g CSF [Na + ] and hypothalamic aldosterone and corticosterone Aldosterone ng/g Corticosterone 8 p<.5 vs others Icv acsf Icv Na + rich acsf for 2 weeks
9 Enhanced BP to CSF [Na + ] in Dahl S vs R 9 mm mhg Resting MAP a 16 mm 18 CSF [Na + ] a a Dahl R Dahl S 12 Dahl R Dahl S acsf acsf with.8 M Na, icv for 2 weeks p<.5 vs other a: p<.5 vs acsf (Huang et al. Am J Physiol 21)
10 1 Activation of neural mechanisms by high salt in Dahl S Genetic dysregulation of CNS Na + -homeostasis : Enhanced Na + - transport from blood into CSF CNS aldosterone Neuronal activation Sympathetic activity Hypertension
11 11 Functional role of aldosterone o e in the CNS Central MR Blockade Limitations: not specific for aldosterone not specific for locally produced steroid Aldosterone synthase inhibition 1vs2 MR activation due to locally 1 vs 2 MR activation due to locally produced aldosterone.
12 12 Aldosterone synthase inhibitor N N (+)-(5R)-4-(5,6,7,8-terahydroimidazo[1,5-a]pyridin-5-yl) benzonitrile hydrochloride FAD 286 is a single (+) -enantiomer C N (Fiebeler et al. Circulation 25)
13 CSF [Na + ] and hypothalamic aldosterone and corticosterone Central aldosterone synthase inhibition 13 pg/g Aldosterone Corticosterone a ng/g Icv acsf Icv Na + rich acsf Icv acsf Icv Na + rich acsf +veh AS inh +veh AS inh p<.5 vs others 1 µg/kg/day
14 % restin ng mmhg bpm 3 CSF [Na+] and sympathetic activity Air Stress RSNA MAP HR acsf a Na + -rich acsf Central aldosterone synthase inhibition Ch hanges in RS SNA (%) Baroreflex control of RSNA 1 Max. slope (%/mmhg) CSF 3.6±.2 CSF AS inh 3.7±.3 (Na)aCSF 2.3±.3 (Na)aCSF AS inh 3.3±.3 p<.5, vs acsf with/without AS inh; a: p<.5, vs Na+ -rich acsf+veh p<.5, vs others 14
15 Dahl S on HNa for 4 weeks 15 Central aldosterone synthase inhibition 4 3 Aldosterone Corticosterone t a pg/g 2 ng/g RNa +veh HNa AS inh RNa HNa RNa HNa +veh AS inh 8 µg/kg/day
16 16 BP and HR in Dahl S on high salt Central aldosterone synthase inhibitor vs MR blocker Resting MAP Resting HR MAP (m mmhg) b 8 µg/kg g/d 8 µg/kg g/d HR (b bpm) µg/kg/d 8 µg/kg/d 1 icv acsf AS inh spir 3 icv acsf AS inh spir p<.5 vs others b: vs RNa+aCSF RNa HNa
17 17 CONCLUSION Central blockade of aldosterone synthesis or MR prevents to a large extent the salt-induced hypertension in Dahl S. locally in the CNS produced aldosterone via MR plays a major role New Paradigm: High salt diet via CSF [Na + ] activatesates aldosterone MR and sodium transport in the CNS.
18 Shift in Paradigm from 18 Old Paradigm: Kidney to CNS Intrinsic changes in renal function lead to a defect in the kidneys ability to excrete salt and to an increase in BP until sodium balance is restored. "the Guyton Dogma" New Paradigm: Kidneys of genetic models of salt induced hypertension do not require hypertension, and the animals live happy (happier?) without. Kidneys are a "sensor and /or effector" organ like the arteries and the heart, and in general the CNS determines the set point of BP.
19 19 Changing g Face of CHF Past and Present Hypertension LVH LV dysfunction CHF Present and Future Hypertension Dyslipidemia Diabetes Smoking Atherosclerosis MI LV remodeling/dysfunction CHF
20 ALLHAT 2 CHF mortality still very high (Davis et al. Circulation, 26)
21 21 LV remodeling following MI
22 Stimuli for cardiac remodeling post MI 22 Cardio-centric view: diastolic wall stress systolic wall stress progressive LV dilation and hypertrophy Cardio-renal renal view: reduced cardiac output and renal perfusion activation of circulatory RAAS salt and water retention Neuro-hormonal view: sympathetic hyperactivity circulatory, cardiac, renal RAAS vasopressin pro-inflammatory cytokines
23 23 CNS and CHF Post MI Brain RAAS: locally yp produced aldosterone MR & AT 1 rec stimulation sympathetic activity & other peripheral mechanisms cardiac remodeling / dysfunction post MI
24 24 Myocardial Infarction Circulation Aldosterone Local Synthesis AS inh Min. Cort. Receptor (-) Spironolactone Ang II (-) Losartan / Transgenic Rats Peripheral Mechanisms CHF
25 25 Transgenic Rats To assess the role of Angiotensins locally produced in the brain Glial fibrillary acidic protein promoter Angiotensinogen Antisense DNA Angiotensinogen antisense RNA (glia only) Angiotensinogen mrna Angiotensinogen SD TG Rats Hypothalamic Angiotensinogen, g pmol/mg protein Plasma Angiotensinogen, g nmol/ml (Schinke et al. PNAS, 1999 )
26 26 pg/g CNS aldosterone post MI Central aldosterone synthase inhibitor 2 weeks +69% Hypothalamus weeks a pg/mg Hippocampus 4 weeks a Sham MI Sham sham MI MI Icv Icv veh AS inh sham MI MI Icv veh Icv AS inh p.5
27 27 Sympathetic Hyperactivity in CHF post MI set point reactivity baroreflex-control
28 Blockade of Brain MR AT 1 -rec prevents sympathetic hyperactivity post MI 2 Air-stress Resting RSNA 3 % res sting mv 1 4. Maximal Gain of baroreflex Sham ---- MI Veh Spir icv -% / mmhg 2. Sham ---- MI Veh Spir Los icv (Francis et al. AJP, 23) (Huang et al. AJP, 25)
29 Blockade of brain RAAS prevents plasma Ang II and aldosterone post tmi 29 Sham MI Sham MI MI & ICV Spironolactone ng g/ ml Plasma Ang II SD TG pg/ ml Plasma Aldosterone p<.5 vs other (Wang et al. Circ Res, 24) (Lal et al. Card vasc Res, 24)
30 Blockade of brain RAAS prevents LV aldosterone post MI 3 pg/m mg TG rats Sham MI Wistar rats with icv spironolactone Sham MI MI & ICV Spironolactone (Lal et al. JMCC, 25) SD TG Rats Wistar rats p<.5 vs other
31 Blockade of brain MR prevents plasma TNF α post MI 31 (pg/m ml) TNF-α CHF-spiro.(n=8) CHF-VEH (n=6) SHAM-VEH (n=7) SHAM-spiro.(n=6) Pre 24hr day 3 day 5 wk 1 wk 2 wk 3 M.I. Spiro. p<.5, vs other (Francis et al, AJP, 24)
32 32 CNS and CHF Post MI Brain RAAS: locally yp produced aldosterone MR & AT 1 rec stimulation sympathetic activity & other peripheral mechanisms cardiac remodeling / dysfunction post MI
33 33 Parameters aa eteso of LV remodeling LV diameter cardiomyocyte numbers and size extracellular l matrix - collagen Parameters of LV dysfunction and CHF LVEDP, LVPSP, LV dp/dt max lung weight RV weight and diameter
34 LV dimensions at 4 weeks post MI Central Blockades 34 Sham MI icv veh MI icv AS inh Diastolic Systolic EF (%) (mm) a 6 4 a 8 6 a (m mm) a a a a p<.5 vs sham; a p<.5 vs MI +veh Sham MI icv veh MI icv los MI icv spir
35 LV pressure-volume curves in transgenic vs. SD rats at 8 wks post MI 35 LV Press sure (mm mhg) # TG-MI TG-Sham SD-MI 2.5 SD-Sham LV Volume (ml/kg) P<.5 vs sham; # P<.5 vs SD MI M I size : 4 ± 3 for TG and 4 ± 4 for SD (Wang et al. Circ Res, 24)
36 Interstitial Fibrosis in Peri-infarct infarct Zone Effect of central MR blocker Interstitial fibrosis (magnification X4) 36 Fibrillar collagen by SEM (magnification X8) Sham MI MI + Icv Spironolactone (Lal et al. Card vasc Res, 24)
37 13 Oral vs icv spironolactone and MI-Induced Induced changes in hemodynamics LVPSP LVEDP 2 12 a a 1 1 a Oral ICV Oral ICV 6 LV +dp/dt max 5 4 a a Sham MI + Vehicle MI + Spironolactone 3 p<.5 vs sham; a p<.5 vs MI+Vehicle Oral ICV (Lal et al. Card vasc Res, 24)
38 LV function at 4 weeks post MI 38 Icv losartan versus icv spironolactone LVPSP LVEDP dp/dt max ) (mmhg a a a a (mmhg g/s) a a p<.5 vs sham; a p<.5 vs MI +veh Sham MI icv veh MI icv los MI icv spir (Huang et al. JMCC 27)
39 LV function 4 weeks post MI Central aldosterone synthase inh 39 LVPSP LVEDP dp/dt max ) (mmhg 14 a a a a a a Sham MI icv veh MI icv AS inh p<.5 vs sham; a p<.5 vs MI +veh
40 4 CNS and LV dysfunction post MI 1 5 CNS RAAS Pre MI 1 day Post MI Clinical CHF weeks/months
41 bpm mmhg % resting Sympathetic activity post MI Air Stress RSNA a 25 2 MAP a 15 a 1 5 HR Sham a MI a a Veh L15 L1 Effects of systemic losartan ges in RSNA (% %) Chan MAP (mmhg) Maximal Slope (%) Sham 3.4±.2 Veh 2.1±.2 L15 2.8±.2a L1 3.4±.3 (Huang et al. JMCC, 27) 41
42 Losartan and sympathetic activity in patients with CHF MSNA Plasma Norepinephrine 42 # 8 2 beats) (burs sts/ (pg/ml) # losartan 5 mg/day losartan 2 mg/day # p<.5 vs baseline + p<.5 compared to losartan 5 mg/day (Ruzicka et al. ESC, 27)
43 The Brain: The forgotten target in Heart Failure 43 Brain RAAS SFO Ouabain Cytokines Cardiac afferents PVN SON LC RVLM Circulating RAAS Sympathetic hyperactivity BP Cytokines Circulating RAAS Cardiac RAAS Cytokines Remodeling Dysfunction vasopressin (Leenen. Circ Res, 27) Other factors? HEART FAILURE
Heart Failure. Acute. Plasma [NE] (pg/ml) 24 Hours. Chronic
Heart Failure Heart failure is the inability of the heart to deliver sufficient blood to the tissues to ensure adequate oxygen supply. Clinically it is characterized by signs of volume overload or symptoms
More informationCritical role of CNS effects of aldosterone in cardiac remodeling post-myocardial infarction in rats
Cardiovascular Research 64 (2004) 437 447 www.elsevier.com/locate/cardiores Abstract Critical role of CNS effects of aldosterone in cardiac remodeling post-myocardial infarction in rats Avtar Lal a, John
More informationBlood Pressure Fox Chapter 14 part 2
Vert Phys PCB3743 Blood Pressure Fox Chapter 14 part 2 T. Houpt, Ph.D. 1 Cardiac Output and Blood Pressure How to Measure Blood Pressure Contribution of vascular resistance to blood pressure Cardiovascular
More informationBlood Pressure Regulation 2. Faisal I. Mohammed, MD,PhD
Blood Pressure Regulation 2 Faisal I. Mohammed, MD,PhD 1 Objectives Outline the intermediate term and long term regulators of ABP. Describe the role of Epinephrine, Antidiuretic hormone (ADH), Renin-Angiotensin-Aldosterone
More informationBlood Pressure Regulation 2. Faisal I. Mohammed, MD,PhD
Blood Pressure Regulation 2 Faisal I. Mohammed, MD,PhD 1 Objectives Outline the intermediate term and long term regulators of ABP. Describe the role of Epinephrine, Antidiuretic hormone (ADH), Renin-Angiotensin-Aldosterone
More informationDefinition of Congestive Heart Failure
Heart Failure Definition of Congestive Heart Failure A clinical syndrome of signs & symptoms resulting from the heart s inability to supply adequate tissue perfusion. CHF Epidemiology Affects 4.7 million
More informationSpecial Lecture 11/08/2013. Hypertension Dr. HN Mayrovitz
Special Lecture 11/08/2013 Hypertension Dr. HN Mayrovitz Arterial Blood Pressure (ABP) Major Factors Summarized Sympathetic Hormones Arteriole MAP ~ Q x TPR + f (V / C) SV x HR Renal SBP Hypertension =
More informationTherefore MAP=CO x TPR = HR x SV x TPR
Regulation of MAP Flow = pressure gradient resistance CO = MAP TPR Therefore MAP=CO x TPR = HR x SV x TPR TPR is the total peripheral resistance: this is the combined resistance of all blood vessels (remember
More informationLXIV: DRUGS: 4. RAS BLOCKADE
LXIV: DRUGS: 4. RAS BLOCKADE ACE Inhibitors Components of RAS Actions of Angiotensin i II Indications for ACEIs Contraindications RAS blockade in hypertension RAS blockade in CAD RAS blockade in HF Limitations
More informationRenal Denervation. Henry Krum MBBS PhD FRACP. Centre of Cardiovascular Research & Monash University/Alfred Hospital;
Renal Denervation Henry Krum MBBS PhD FRACP Centre of Cardiovascular Research & Education in Therapeutics, Monash University/Alfred Hospital; Alfred Heart Centre, The Alfred Hospital, Melbourne Australia
More informationVeins. VENOUS RETURN = PRELOAD = End Diastolic Volume= Blood returning to heart per cardiac cycle (EDV) or per minute (Venous Return)
Veins Venous system transports blood back to heart (VENOUS RETURN) Capillaries drain into venules Venules converge to form small veins that exit organs Smaller veins merge to form larger vessels Veins
More informationOptimal blockade of the Renin- Angiotensin-Aldosterone. in chronic heart failure
Optimal blockade of the Renin- Angiotensin-Aldosterone Aldosterone- (RAA)-System in chronic heart failure Jan Östergren Department of Medicine Karolinska University Hospital Stockholm, Sweden Key Issues
More informationSalt Sensitivity: Mechanisms, Diagnosis, and Clinical Relevance
Salt Sensitivity: Mechanisms, Diagnosis, and Clinical Relevance Matthew R. Weir, MD Professor and Director Division of Nephrology University of Maryland School of Medicine Overview Introduction Mechanisms
More informationCKD Satellite Symposium
CKD Satellite Symposium Recommended Therapy by Heart Failure Stage AHA/ACC Task Force on Practice Guideline 2001 Natural History of Heart Failure Patients surviving % Mechanism of death Sudden death 40%
More informationBing S. Huang,* Sara Ahmadi,* Monir Ahmad,* Roselyn A. White, and Frans H. H. Leenen
Am J Physiol Heart Circ Physiol 299: H422 H430, 2010. First published May 28, 2010; doi:10.1152/ajpheart.00256.2010. Central neuronal activation and pressor responses induced by circulating ANG II: role
More informationBlood Pressure Regulation. Slides 9-12 Mean Arterial Pressure (MAP) = 1/3 systolic pressure + 2/3 diastolic pressure
Sheet physiology(18) Sunday 24-November Blood Pressure Regulation Slides 9-12 Mean Arterial Pressure (MAP) = 1/3 systolic pressure + 2/3 diastolic pressure MAP= Diastolic Pressure+1/3 Pulse Pressure CO=MAP/TPR
More informationIn the name of GOD. Animal models of cardiovascular diseases: myocardial infarction & hypertension
In the name of GOD Animal models of cardiovascular diseases: myocardial infarction & hypertension 44 Presentation outline: Cardiovascular diseases Acute myocardial infarction Animal models for myocardial
More informationRegulation of Arterial Blood Pressure 2 George D. Ford, Ph.D.
Regulation of Arterial Blood Pressure 2 George D. Ford, Ph.D. OBJECTIVES: 1. Describe the Central Nervous System Ischemic Response. 2. Describe chemical sensitivities of arterial and cardiopulmonary chemoreceptors,
More informationCardiovascular Protection and the RAS
Cardiovascular Protection and the RAS Katalin Kauser, MD, PhD, DSc Senior Associate Director, Boehringer Ingelheim Pharmaceutical Inc. Micardis Product Pipeline Scientific Support Ridgefield, CT, USA Cardiovascular
More informationCatheter Based Denervation for Heart Failure
Catheter Based Denervation for Heart Failure David E. Kandzari, MD, FACC, FSCAI Chief Scientific Officer Director, Interventional Cardiology Piedmont Heart Institute Atlanta, Georgia david.kandzari@piedmont.org
More informationDr. Khairy Abdel Dayem. Professor of Cardiology Ain-Shams University
Dr. Khairy Abdel Dayem Professor of Cardiology Ain-Shams University RALES Randomized Aldactone Evaluation Study 1. NEJM 1999 2. Bertram Pitt 3. 1660 Class III and IV HF patients 4. EF 35% 5. 841 placebo
More informationEntresto Development of sacubitril/valsartan (LCZ696) for the treatment of heart failure with reduced ejection fraction
Cardio-Metabolic Franchise Entresto Development of sacubitril/valsartan (LCZ696) for the treatment of heart failure with reduced ejection fraction Randy L Webb, PhD Rutgers Workshop October 21, 2016 Heart
More informationDisclosure of Relationships
Disclosure of Relationships Over the past 12 months Dr Ruilope has served as Consultant and Speakers Bureau member of Astra-Zeneca, Bayer, Daiichi-Sankyo, Menarini, Novartis, Otsuka, Pfizer, Relypsa, Servier
More informationCASE 13. What neural and humoral pathways regulate arterial pressure? What are two effects of angiotensin II?
CASE 13 A 57-year-old man with long-standing diabetes mellitus and newly diagnosed hypertension presents to his primary care physician for follow-up. The patient has been trying to alter his dietary habits
More informationAntialdosterone treatment in heart failure
Update on the Treatment of Chronic Heart Failure 2012 Antialdosterone treatment in heart failure 전남의대윤현주 Chronic Heart Failure Prognosis of Heart failure Cecil, Text book of Internal Medicine, 22 th edition
More informationCirculation. Blood Pressure and Antihypertensive Medications. Venous Return. Arterial flow. Regulation of Cardiac Output.
Circulation Blood Pressure and Antihypertensive Medications Two systems Pulmonary (low pressure) Systemic (high pressure) Aorta 120 mmhg Large arteries 110 mmhg Arterioles 40 mmhg Arteriolar capillaries
More informationSPECIAL PATHOPHYSIOLOGY HYPERTENSION
SPECIAL PATHOPHYSIOLOGY HYPERTENSION 1. Systolic blood pressure is elevated when it is over: 1. 120mmHg. 2. 130mmHg. 3. 160mmHg. 4. 140mmHg. 5. 150mmHg. 2. Diastolic blood pressure is elevated when it
More informationAldosterone Antagonism in Heart Failure: Now for all Patients?
Aldosterone Antagonism in Heart Failure: Now for all Patients? Inder Anand, MD, FRCP, D Phil (Oxon.) Professor of Medicine, University of Minnesota, Director Heart Failure Program, VA Medical Center 111C
More informationDrugs acting on the reninangiotensin-aldosterone
Drugs acting on the reninangiotensin-aldosterone system John McMurray Eugene Braunwald Scholar in Cardiovascular Diseases, Brigham and Women s Hospital, Boston & Visiting Professor, Harvard Medical School
More informationDIASTOLIC HEART FAILURE
DIASTOLIC HEART FAILURE M Mohsen Ibrahim, MD Alexandria, Proposed Criteria for Diastolic Heart Failure ESC Working Group (EHJ 1998) CHF signs/symptoms EF 45% Hemodynamic or echo evidence of diastolic dysfunction
More informationTreating Heart Failure in Biodiverse Patient Populations: Best Practices and Unveiling Disparities in Blacks
Treating Heart Failure in Biodiverse Patient Populations: Best Practices and Unveiling Disparities in Blacks 12th Annual Leadership Summit on Health Disparities & Congressional Black Caucus Spring Health
More informationRisk Stratification in Heart Failure: The Role of Emerging Biomarkers
Risk Stratification in Heart Failure: The Role of Emerging Biomarkers David G. Grenache, PhD Associate Professor of Pathology, University of Utah Medical Director, ARUP Laboratories Salt Lake City, UT
More informationPre-discussion questions
Amanda Bartlett, PA-C Dustin Bartlett, PA-C Andrea Applegate, PA-C Leslie Yearta Brown, NP CHF Round Table Discussion Objectives ANDREA- Discuss the definition and different categories of CHF DUSTIN- Define
More informationCopyright 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Normal Cardiac Anatomy
Mosby,, an affiliate of Elsevier Normal Cardiac Anatomy Impaired cardiac pumping Results in vasoconstriction & fluid retention Characterized by ventricular dysfunction, reduced exercise tolerance, diminished
More informationAldosterone synthase inhibitors. John McMurray BHF Cardiovascular Research Centre University of Glasgow
Aldosterone synthase inhibitors John McMurray BHF Cardiovascular Research Centre University of Glasgow Inhibition of aldosterone synthesis is hypothesized to be of benefit to patients with cardiovascular
More informationHYPERTENSION: Sustained elevation of arterial blood pressure above normal o Systolic 140 mm Hg and/or o Diastolic 90 mm Hg
Lecture 39 Anti-Hypertensives B-Rod BLOOD PRESSURE: Systolic / Diastolic NORMAL: 120/80 Systolic = measure of pressure as heart is beating Diastolic = measure of pressure while heart is at rest between
More informationCardiovascular System B L O O D V E S S E L S 2
Cardiovascular System B L O O D V E S S E L S 2 Blood Pressure Main factors influencing blood pressure: Cardiac output (CO) Peripheral resistance (PR) Blood volume Peripheral resistance is a major factor
More informationThe Cardiovascular System and Aging- Is it Built to Fail?
The Cardiovascular System and Aging- Is it Built to Fail? Francis G. Spinale, MD, PhD Professor of Surgery and Cell Biology and Anatomy University of South Carolina School of Medicine Veterans Affairs
More informationAnalysis of AVP functions via V1a and V1b receptors with knockout mice. Akito Tanoue
Analysis of AVP functions via V1a and V1b receptors with knockout mice Akito Tanoue Department of Pharmacology, National Research Institute for Child Health and Development Arginine-Vasopressin (AVP) is
More informationRenal Regulation of Sodium and Volume. Dr. Dave Johnson Associate Professor Dept. Physiology UNECOM
Renal Regulation of Sodium and Volume Dr. Dave Johnson Associate Professor Dept. Physiology UNECOM Maintaining Volume Plasma water and sodium (Na + ) are regulated independently - you are already familiar
More informationBIPN100 F15 Human Physiology (Kristan) Lecture 18: Endocrine control of renal function. p. 1
BIPN100 F15 Human Physiology (Kristan) Lecture 18: Endocrine control of renal function. p. 1 Terms you should understand by the end of this section: diuresis, antidiuresis, osmoreceptors, atrial stretch
More informationThe Therapeutic Potential of Novel Approaches to RAAS. Professor of Medicine University of California, San Diego
The Therapeutic Potential of Novel Approaches to RAAS Inhibition in Heart Failure Barry Greenberg, M.D. Professor of Medicine University of California, San Diego Chain of Events Leading to End-Stage Heart
More informationHypertension Update Warwick Jaffe Interventional Cardiologist Ascot Hospital
Hypertension Update 2008 Warwick Jaffe Interventional Cardiologist Ascot Hospital Definition of Hypertension Continuous variable At some point the risk becomes high enough to justify treatment Treatment
More informationRAS Blockade Across the CV Continuum
A Summary of Recent International Meetings RAS Blockade Across the CV Continuum Copyright New Evidence Presented at the 2009 Congress of the European Society of Cardiology (August 29-September 2, Barcelona)
More informationHeart Failure: Combination Treatment Strategies
Heart Failure: Combination Treatment Strategies M. McDonald MD, FRCP State of the Heart Symposium May 28, 2011 None Disclosures Case 69 F, prior MIs (LV ejection fraction 25%), HTN No demonstrable ischemia
More informationHeart Failure (HF) Treatment
Heart Failure (HF) Treatment Heart Failure (HF) Complex, progressive disorder. The heart is unable to pump sufficient blood to meet the needs of the body. Its cardinal symptoms are dyspnea, fatigue, and
More informationHypertension Management Focus on new RAAS blocker. Disclosure
Hypertension Management Focus on new RAAS blocker Rameshkumar Raman M.D Endocrine Associates of The Quad Cities Disclosure Speaker bureau Abbott, Eli Lilly, Novo Nordisk, Novartis, Takeda, Merck, Solvay
More informationLab Period: Name: Physiology Chapter 14 Blood Flow and Blood Pressure, Plus Fun Review Study Guide
Lab Period: Name: Physiology Chapter 14 Blood Flow and Blood Pressure, Plus Fun Review Study Guide Main Idea: The function of the circulatory system is to maintain adequate blood flow to all tissues. Clinical
More informationExercise in Adverse Cardiac Remodeling: of Mice and Men
Exercise in Adverse Cardiac Remodeling: of Mice and Men 17-01-2013 Dirk J Duncker Experimental Cardiology, Cardiology, Thoraxcenter Cardiovascular Research Institute COEUR Erasmus MC, University Medical
More informationPathophysiology: Heart Failure
Pathophysiology: Heart Failure Mat Maurer, MD Irving Assistant Professor of Medicine Outline Definitions and Classifications Epidemiology Muscle and Chamber Function Pathophysiology Heart Failure: Definitions
More informationAutonomic regulation therapy for heart failure
Autonomic regulation therapy for heart failure Pre-clinical and Clinical Evidence Supporting Vagus Nerve Stimulation For Treatment of Heart Failure Inder Anand, MD, FRCP, D Phil, (Oxon.) Professor of Medicine,
More informationHypertension and diabetic nephropathy
Hypertension and diabetic nephropathy Elisabeth R. Mathiesen Professor, Chief Physician, Dr sci Dep. Of Endocrinology Rigshospitalet, University of Copenhagen Denmark Hypertension Brain Eye Heart Kidney
More informationInteractionofInflammatoryResponseandSympatheticNervousSystemintheCentralRegulationofChronicHeartFailureinRats
: I Surgeries and Cardiovascular System Volume 16 Issue 4 Version 1.0 Year 2016 Type: Double Blind Peer Reviewed International Research Journal Publisher: Global Journals Inc. (USA) Online ISSN: 2249-4618
More informationRegulation of Body Fluids: Na + and Water Linda Costanzo, Ph.D.
Regulation of Body Fluids: Na + and Water Linda Costanzo, Ph.D. OBJECTIVES: After studying this lecture, the student should understand: 1. Why body sodium content determines ECF volume and the relationships
More informationSystemic Hypertension Dr ahmed almutairi Assistant professor Internal medicine dept
Systemic Hypertension Dr ahmed almutairi Assistant professor Internal medicine dept Continents 1- introduction 2- classification/definition 3- classification/etiology 4-etiology in both categories 5- complications
More informationPreserved EF with heart failure (HF pef) 50% 5 year survival. Both have type 2 diabetes Both have hypertension Both have normal ejection fractions
Research companies Government / University research Preserved EF with heart failure (HF pef) 50% 5 year survival Both have type 2 diabetes Both have hypertension Both have normal ejection fractions Introduction
More informationIn Vivo Animal Models of Heart Disease. Why Animal Models of Disease? Timothy A Hacker, PhD Department of Medicine University of Wisconsin-Madison
In Vivo Animal Models of Heart Disease Timothy A Hacker, PhD Department of Medicine University of Wisconsin-Madison Why Animal Models of Disease? Heart Failure (HF) Leading cause of morbidity and mortality
More informationCardiovascular System. Heart
Cardiovascular System Heart Electrocardiogram A device that records the electrical activity of the heart. Measuring the relative electrical activity of one heart cycle. A complete contraction and relaxation.
More informationCardiovascular Disease in CKD. Parham Eftekhari, D.O., M.Sc. Assistant Clinical Professor Medicine NSUCOM / Broward General Medical Center
Cardiovascular Disease in CKD Parham Eftekhari, D.O., M.Sc. Assistant Clinical Professor Medicine NSUCOM / Broward General Medical Center Objectives Describe prevalence for cardiovascular disease in CKD
More informationNora Goldschlager, M.D. SFGH Division of Cardiology UCSF
CLASSIFICATION OF HEART FAILURE Nora Goldschlager, M.D. SFGH Division of Cardiology UCSF DISCLOSURES: NONE CLASSIFICATION C OF HEART FAILURE NYHA I IV New paradigm Stage A: Pts at high risk of developing
More informationWhen should you treat blood pressure in the young?
ESC Stockholm - Dilemmas in Cardiovascular Disease Prevention in the Young: 30 th August 2010 When should you treat blood pressure in the young? Bryan Williams MD FRCP FAHA FESC Professor of Medicine Department
More informationLeft ventricular hypertrophy: why does it happen?
Nephrol Dial Transplant (2003) 18 [Suppl 8]: viii2 viii6 DOI: 10.1093/ndt/gfg1083 Left ventricular hypertrophy: why does it happen? Gerard M. London Department of Nephrology and Dialysis, Manhes Hospital,
More informationVALUE OF ACEI IN THE MANAGEMENT OF HYPERTENSION
VALUE OF ACEI IN THE MANAGEMENT OF HYPERTENSION Dr Catherine BESEME Paris 6 th December 2005 6 th International Congress of Bangladesh Society of Medicine Hypertension is a risk factor at the source, with
More informationDoppler ultrasound, see Ultrasonography. Magnetic resonance imaging (MRI), kidney oxygenation assessment 75
Subject Index Acidemia, cardiorenal syndrome type 3 146 Acute Dialysis Quality Initiative (ADQI) acute kidney injury biomarkers, see Acute kidney injury; specific biomarkers cardiorenal syndrome, see specific
More informationANGIOTENSIN II RECEPTOR BLOCKERS: MORE THAN THE ALTERNATIVE PRESENTATION BY: PATRICK HO, USC PHARM D. CANDIDATE OF 2017 MENTOR: DR.
ANGIOTENSIN II RECEPTOR BLOCKERS: MORE THAN THE ALTERNATIVE PRESENTATION BY: PATRICK HO, USC PHARM D. CANDIDATE OF 2017 MENTOR: DR. CRAIG STERN, PHARMD, MBA, RPH, FASCP, FASHP, FICA, FLMI, FAMCP RENIN-ANGIOTENSIN
More informationheart failure John McMurray University of Glasgow.
A to Z of RAAS blockade in heart failure John McMurray BHF Cardiovascular Research Centre University of Glasgow. RAAS inhibition in CHF ACE inhibition in patients with low LVEF CHF CONSENSUS Enalapril
More informationMetabolic Syndrome and Chronic Kidney Disease
Metabolic Syndrome and Chronic Kidney Disease Definition of Metabolic Syndrome National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III Abdominal obesity, defined as a waist circumference
More information- Dr Alia Shatnawi. 1 P a g e
- 1 مها أبو عجمية - - - Dr Alia Shatnawi 1 P a g e A Skippable Intr0 Blood pressure normally decreases during the night. Absence of this phenomenon is called (nondipping) Wikipedia: Circadian rhythm....
More informationrenoprotection therapy goals 208, 209
Subject Index Aldosterone, plasminogen activator inhibitor-1 induction 163, 164, 168 Aminopeptidases angiotensin II processing 64 66, 214 diabetic expression 214, 215 Angiotensin I intrarenal compartmentalization
More informationMonday, 17 April 2017 BODY FLUID HOMEOSTASIS
Monday, 17 April 2017 BODY FLUID HOMEOSTASIS Phenomenon: shipwrecked sailor on raft in ocean ("water, water everywhere but not a drop to drink") Why are the sailors thirsty? (What stimulated thirst?) Why
More informationLV geometric and functional changes in VHD: How to assess? Mi-Seung Shin M.D., Ph.D. Gachon University Gil Hospital
LV geometric and functional changes in VHD: How to assess? Mi-Seung Shin M.D., Ph.D. Gachon University Gil Hospital LV inflow across MV LV LV outflow across AV LV LV geometric changes Pressure overload
More informationOutline. Pathophysiology: Heart Failure. Heart Failure. Heart Failure: Definitions. Etiologies. Etiologies
Outline Pathophysiology: Mat Maurer, MD Irving Assistant Professor of Medicine Definitions and Classifications Epidemiology Muscle and Chamber Function Pathophysiology : Definitions An inability of the
More informationMetoprolol Succinate SelokenZOC
Metoprolol Succinate SelokenZOC Blood Pressure Control and Far Beyond Mohamed Abdel Ghany World Health Organization - Noncommunicable Diseases (NCD) Country Profiles, 2014. 1 Death Rates From Ischemic
More informationMechanism: 1- waterretention from the last part of the nephron which increases blood volume, venous return EDV, stroke volume and cardiac output.
Blood pressure regulators: 1- Short term regulation:nervous system Occurs Within secondsof the change in BP (they are short term because after a while (2-3 days) they adapt/reset the new blood pressure
More informationBIPN100 F15 Human Physiol I (Kristan) Lecture 14 Cardiovascular control mechanisms p. 1
BIPN100 F15 Human Physiol I (Kristan) Lecture 14 Cardiovascular control mechanisms p. 1 Terms you should understand: hemorrhage, intrinsic and extrinsic mechanisms, anoxia, myocardial contractility, residual
More informationChapter 19 The Urinary System Fluid and Electrolyte Balance
Chapter 19 The Urinary System Fluid and Electrolyte Balance Chapter Outline The Concept of Balance Water Balance Sodium Balance Potassium Balance Calcium Balance Interactions between Fluid and Electrolyte
More informationReal World Experience with Renal Denervation Therapy
JCR 2013 Real World Experience with Renal Denervation Therapy Seung-Hyuk Choi Division of Cardiology Samsung Medical Center Seoul, Korea Hypertension A Major Public Health Burden Astonishing prevalence
More information3/10/2009 VESSELS PHYSIOLOGY D.HAMMOUDI.MD. Palpated Pulse. Figure 19.11
VESSELS PHYSIOLOGY D.HAMMOUDI.MD Palpated Pulse Figure 19.11 1 shows the common sites where the pulse is felt. 1. Temporal artery at the temple above and to the outer side of the eye 2. External maxillary
More informationCardiorenal and Renocardiac Syndrome
And Renocardiac Syndrome A Vicious Cycle Cardiorenal and Renocardiac Syndrome Type 1 (acute) Acute HF results in acute kidney injury Type 2 Chronic cardiac dysfunction (eg, chronic HF) causes progressive
More informationFaiez Zannad. Institut Lorrain du Coeur et des Vaisseaux. CIC - Inserm
Faiez Zannad Institut Lorrain du Coeur et des Vaisseaux CIC - Inserm Disclosure Faiez Zannad Grants BG Medicine, Roche Diagnostics. Consultant/Steering committees/event committees/ Data safety Monitoring
More informationCopeptin in heart failure: Associations with clinical characteristics and prognosis
Copeptin in heart failure: Associations with clinical characteristics and prognosis D. Berliner, N. Deubner, W. Fenske, S. Brenner, G. Güder, B. Allolio, R. Jahns, G. Ertl, CE. Angermann, S. Störk for
More informationRelevance of sympathetic overactivity in hypertension and heart failure Therapeutic Implications
Relevance of sympathetic overactivity in hypertension and heart failure Therapeutic Implications Uta C. Hoppe, MD, FESC Dep. of Internal Medicine II Paracelsus University Salzburg Austria Disclosures Within
More informationPresenter: Tom Mulvey
Slides are from Level 3 Biology Course Content Day, 7 th November 2012 Presenter: Tom Mulvey Teachers are free to use these for teaching purposes with appropriate acknowledgement Blood Pressure Ways of
More informationBlood Pressure Regulation -1
CVS Physiology Lecture 18 Blood Pressure Regulation -1 Please study the previous sheet before studying this one, even if the first part in this sheet is revision. In the previous lecture we were talking
More informationHeart Failure with Preserved Ejection Fraction: Mechanisms and Management
Heart Failure with Preserved Ejection Fraction: Mechanisms and Management Jay N. Cohn, M.D. Professor of Medicine Director, Rasmussen Center for Cardiovascular Disease Prevention University of Minnesota
More informationSUPPLEMENTARY DATA. Supplementary Table 1. Baseline Patient Characteristics
Supplementary Table 1. Baseline Patient Characteristics Normally distributed data are presented as mean (±SD), data that were not of a normal distribution are presented as median (ICR). The baseline characteristics
More informationCardiovascular Pharmacotherapy
Cardiovascular Pharmacotherapy Overview Mechanism of cardiovascular drugs Indications and clinical use in cardiology Renin-Angiotensin Inhibitors: Angiotensin-Converting Enzyme Inhibitors, Angiotensin
More informationΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ ΚΑΙ ΑΝΤΑΓΩΝΙΣΤΕΣ ΑΛΔΟΣΤΕΡΟΝΗΣ ΣΠΥΡΟΜΗΤΡΟΣ ΓΕΩΡΓΙΟΣ MD, FESC. E.Α Κ/Δ Γ.Ν.ΚΑΤΕΡΙΝΗΣ
ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ ΚΑΙ ΑΝΤΑΓΩΝΙΣΤΕΣ ΑΛΔΟΣΤΕΡΟΝΗΣ ΣΠΥΡΟΜΗΤΡΟΣ ΓΕΩΡΓΙΟΣ MD, FESC. E.Α Κ/Δ Γ.Ν.ΚΑΤΕΡΙΝΗΣ Aldosterone is a mineralocorticoid hormone synthesized by the adrenal glands that has several regulatory
More informationAkash Ghai MD, FACC February 27, No Disclosures
Akash Ghai MD, FACC February 27, 2015 No Disclosures Epidemiology Lifetime risk is > 20% for American s older than 40 years old. > 650,000 new cases diagnosed each year. Incidence increases with age: 2%
More informationHeart failure and diabetes: SGLT-2 inhibition, a paradigm shift?
SGLT-2 inhibition, diabetes and CVD, ESC Rome August 28, 2016 Heart failure and diabetes: SGLT-2 inhibition, a paradigm shift? John McMurray BHF Cardiovascular Research Centre, University of Glasgow &
More informationHypertension is a persistent elevation of B.P. above the normal level. Approximately 1 billion people have hypertension
ISSN: 0975-766X CODEN: IJPTFI Available Online through Research Article www.ijptonline.com STUDY OF LEVEL IN ESSENTIAL HYPERTENSION Krithika Mohanraj 1 *, Dr.R.Rajeswari 2 Bharath University, Chennai.
More informationTherapeutic Targets and Interventions
Therapeutic Targets and Interventions Ali Valika, MD, FACC Advanced Heart Failure and Pulmonary Hypertension Advocate Medical Group Midwest Heart Foundation Disclosures: 1. Novartis: Speaker Honorarium
More informationIntroductory Clinical Pharmacology Chapter 41 Antihypertensive Drugs
Introductory Clinical Pharmacology Chapter 41 Antihypertensive Drugs Blood Pressure Normal = sys
More informationLong-Term Management: Preventing Progression. Daniel Burkhoff Cardiovascular Research Foundation and Columbia University
Long-Term Management: Preventing Progression Daniel Burkhoff Cardiovascular Research Foundation and Columbia University Disclosure Unrestricted institutional (CRF) educational grant from Abiomed Left Ventricular
More informationLaunch Meeting 3 rd April 2014, Lucas House, Birmingham
Angiotensin Converting Enzyme inhibitor (ACEi) / Angiotensin Receptor Blocker (ARB) To STOP OR Not in Advanced Renal Disease Launch Meeting 3 rd April 2014, Lucas House, Birmingham Prof Sunil Bhandari
More informationBODY FLUID. Outline. Functions of body fluid Water distribution in the body Maintenance of body fluid. Regulation of fluid homeostasis
BODY FLUID Nutritional Biochemistry Yue-Hwa Chen Dec 13, 2007 Chen 1 Outline Functions of body fluid Water distribution in the body Maintenance of body fluid Intake vs output Regulation of body fluid Fluid
More informationHypertension. Penny Mosley MRPharmS
Hypertension Penny Mosley MRPharmS Outline of presentation Introduction to hypertension Physiological control of arterial blood pressure What determines our bp? What determines the heart rate? What determines
More informationHeart Failure. Subjective SOB (shortness of breath) Peripheral edema. Orthopnea (2-3 pillows) PND (paroxysmal nocturnal dyspnea)
Pharmacology I. Definitions A. Heart Failure (HF) Heart Failure Ezra Levy, Pharm.D. HF Results when one or both ventricles are unable to pump sufficient blood to meet the body s needs There are 2 types
More informationDysglycaemia and Hypertension. Dr E M Manuthu Physician Kitale
Dysglycaemia and Hypertension Dr E M Manuthu Physician Kitale None Disclosures DM is MI equivalent MR FIT Objective was to assess predictors of CVD mortality among men with and without diabetes and
More informationEffects of Kidney Disease on Cardiovascular Morbidity and Mortality
Effects of Kidney Disease on Cardiovascular Morbidity and Mortality Joachim H. Ix, MD, MAS Assistant Professor in Residence Division of Nephrology University of California San Diego, and Veterans Affairs
More information