Na + /K + interaction in the kidney, blood vessels, brain, and beyond

Transcription

1 Na + /K + interaction in the kidney, blood vessels, brain, and beyond Horacio J. Adrogué, M.D. Professor of Medicine, Baylor College of Medicine Chief, Clinical Nephrology and Hypertension. Houston Methodist Hospital Houston, Texas Workshop on Na + /K + Dietary Reference Intake Health and Medicine Division. The National Academies of Sciences, Engineering, and Medicine Washington, DC

2 Generation of Na + excess and K + deficit: the kidney-modern diet maladaptation Our kidneys are poised to conserve Na + and excrete K + The above served prehistoric humans, who consumed a Na + -poor and K + -rich diet Na + losses were negligible and K + excretion matched intake (at least 90% by the kidney) Such design is unfit today (Na + -rich, K + -poor diet) End result today: body Na + excess and K + deficit in a substantial fraction of the population Adrogué HJ, Madias NE. N Engl J Med 2007;356:

3 Molecular mechanisms implicated in the retention of Na + and loss of K + by the kidneys in primary hypertension Adrogué HJ, Madias NE. N Engl J Med 2007;356:

4 Interaction of the modern western diet and the kidneys in the pathogenesis of primary hypertension Modern Western diet High Na + intake Renal derangements of Na + transport + Low K + intake + Ineffective K + conservation Renal Na + retention Excessive renal/fecal K + loss Body Na + excess Body K + deficit ECF volume expansion Release of DLF Na +, K +, ATPase Cellular Na + excess Cellular K + deficit VSMC contraction Increased peripheral vascular resistance HYPERTENSION Adrogué HJ, Madias NE. N Engl J Med 2007;356:

5 Similar tissue damage and effects develop with mineralocorticoids plus a High-Na + Diet or a High-Na + and Low K + -Diet alone in laboratory animals Kidneys Heart Mineralocorticoid administration plus high-na + diet Arteries High-Na + /low-k + diet (suppression of endogenous mineralocorticoids) Central Nervous System Metabolism and other effects Adrogué HJ, Madias NE. N Engl J Med 2007;356:

6 Molecular pathways implicated in the increased vascular smooth-muscle tone caused by Na + excess and K + deficit in primary hypertension Adrogué HJ, Madias NE. N Engl J Med 2007;356:

7 Molecular pathways implicated in K + -induced, endothelium-dependent vasodilation Endothelial Cell (EC), Intercellular Space (IS), and Smooth Muscle Cell (VSMC) Adrogué HJ, Madias NE. N Engl J Med 2007;356:

8 Effects of extracellular [K + ] and [Na + ] on endothelial cell stiffness F-actin changes to G-actin in the cytoskeleton with activation of NO release Büssemaker E et al. Am J Kidney Dis 2010;55:

9 Adrogué HJ, Madias NE. Journal of the American Society of Hypertension 2014;8: Adrogué HJ, Medias NE. Current Opinion in Nephrology and Hypertension 2017;26:

10 Adrogué HJ, Madias NE. Journal of the American Society of Hypertension 2014;8: Adrogué HJ, Medias NE. Current Opinion in Nephrology and Hypertension2017;26:

11 K+ intake inhibits Na+ sensitivity Morris RC Jr et al. Hypertension 1999;33:18-23.

12 Impact of a low- or high-k + intake on the blood-pressure effects and cardiovascular risk of a high-na + diet High-Na + Diet Low-K + intake General Aggravation of primary and mineralocorticoid hypertension High-K + intake Prevention/amelioration of primary and mineralocorticoid hypertension Reduction in need for antihypertensive medication Increase in Na + sensitivity Inhibition of Na + sensitivity Promotion of positive Na + balance (decreased natriuresis) Promotion of negative Na + balance (increased natriuresis) Partial intracellular replacement of lost K + by retained Na + Displacement of intracellular Na + by retained K + Stimulation of circulating and tissue RAS Depression of baroreceptor sensitivity Suppression of circulating and tissue RAS Restoration of baroreceptor sensitivity Organ-specific Kidney Augmentation of renin release (direct action) Increase in renal vascular resistance Reduction in glomerular filtration rate Promotion of kidney damage: glomerular and arteriolar lesions Promotion of inflammatory pathways of fibrosis Suppression of renin release (direct action) Reduction in renal vascular resistance Increase in glomerular filtration rate Protection from kidney damage Suppression of inflammatory pathways of fibrosis Brain Inhibition of neuronal Na + pump Increase in sympathetic nerve activity Augmentation of central effects of aldosterone Augmentation of central effects of EO Increase risk of cerebrovascular accident Stimulation of neuronal Na + pump Depression of sympathetic nerve activity Suppression of central effects of aldosterone Depression of central effects of EO Protection from cerebrovascular accident Adrogué HJ, Madias NE. Journal of the American Society of Hypertension 2014;8:

13 Thank you