Tubule to Decreased and Increased Renal Perfusion Pressure

Transcription

1 1184 Response of Superficial Proximal Convoluted Tubule to Decreased and Increased Renal Perfusion Pressure In Vivo Microperfusion Study in Rats Yoshikazu Kinoshita and Franklyn G. Knox Although urinary sodium excretion is positively influenced by acute changes in renal perfusion pressure, micropuncture studies show highly conflicting results concerning the response of superficial proximal tubule sodium reabsorption to changes in renal perfusion pressure. In the present study, the changes of superficial proximal reabsorption to decreased and increased renal perfusion pressure were determined in rats by an in vivo microperfusion method. In vivo microperfusion was selected as the method to determine the proximal sodium reabsorption because this method made it possible to deliver a constant fluid and electrolyte load to the proximal tubule without the influence of possible changes of glomerular filtration rate. Renal perfusion pressure was decreased from normal pressure by inflating a suprarenal aortic cuff and was increased from the normal level by the occlusion of celiac and mesenteric arteries and the infrarenal aorta. Although fractional excretion of sodium (FENa) in the urine was decreased from 1.24±0.23% to 0.45±0.11% (n=7, p<0.01) when renal perfusion pressure was decreased from 125±6 to 99±3 mm Hg, absolute tubular reabsorption by the superficial proximal convoluted tubules was not increased (from 4.4±0.5 to 4.2±0.3 nu/min/mm, n=22). When the renal perfusion pressure was elevated from 126±4 to 149±4 mm Hg, tubular reabsorption by the superficial proximal tubules was decreased from 4.1± 0.3 to 2.5±0.3 nl/min/mm (n=36, p<0.01) with an accompanying increase in FENa (from 1.28±0.24% to 2.29±0.37%, n=9, p<o.os). In summary, superficial proximal tubule reabsorption is decreased by increases in renal perfusion pressure but is not affected by decreases in renal perfusion pressure. (Circulation Research 1990;66: ) R enal perfusion pressure (RPP) is well known to play an important role in the regulation of renal sodium and water excretion.1 When RPP is changed, the urinary sodium excretion changes in the same direction without a measurable change of glomerular filtration rate (GFR).1 Although the proximal convoluted tubule has been shown to be one of the nephron segments that contributes to the pressure natriuresis phenomenon, reports concerning the response of superficial proximal tubules to changes in RPP are highly conflicting.2-8 In a micropuncture study in rats, Roman7 From the Nephrology Research Laboratories, Departments of Physiology and Biophysics and Medicine, Mayo Clinic and Foundation, Rochester, Minnesota. Supported by the American Heart Association, Minnesota Affiliate; National Institutes of Health grant HL-14133; and the Mayo Foundation. Address for reprints: Franklyn G. Knox, MD, PhD, Department of Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, MN Received July 21, 1989; accepted November 21, studied the changes of superficial proximal tubular reabsorption when RPP was increased from subnormal levels to high levels. He found that the reabsorption by the superficial proximal tubules was decreased by the elevation of RPP and showed the contribution of this segment in the pressure natriuresis phenomenon. By using an in vivo microperfusion study, Chou and Marsh4 also reported that the tubular reabsorption by the superficial proximal tubule was depressed by the carotid artery occlusioninduced elevation of RPP in rats. On the other hand, rat micropuncture studies performed by Haas et a16 did not find a change in sodium reabsorption by the superficial proximal tubules when RPP was decreased from normal levels by suprarenal aortic constriction. In the present study, individual effects of increased RPP and decreased RPP from normal levels on the superficial proximal reabsorption were determined and compared with each other to test the hypothesis that superficial proximal reabsorption is affected only

2 Kinoshita and Knox Renal Perfusion Pressure and Proximal Tubules 1185 TABLE 1. Effect of Sodium Concentration in the Perfusate on Tubular Reabsorption by Superficial Proximal Convoluted Tubules Length of Tubular flow rate Absolute tubular RPP perfused tubules at collection sites reabsorption (mm Hg) (mm) (nl/min) (nl/min/mm) Group 1 (effect of Na) (n=20) Normal Na (147 mm) 112±4 3.5± ± ±0.4 Low Na (7 mm) 112±4 3.5± * 0.4±0.2* RPP, renal perfusion pressure; n, number of perfused superficial proximal convoluted tubules. *p<0.01, significantly different from values in normal RPP. when RPP is increased above normal levels. In vivo microperfusion was used to determine the proximal sodium reabsorption because this method enabled a constant delivery of a fluid and electrolyte load to proximal tubules without the influence of the possible effect of RPP on GFR. Materials and Methods In Vivo Microperfusion Study Male Sprague-Dawley rats ( g body weight) were used for the experiments. The rats were fed normal rat chow containing 0.1 meq Na/g and had free access to water. All animals were fasted hours before the experiment. The rats were anesthetized with an intraperitoneal injection of 100 mg/kg body wt of 5-sec-butyl-5-ethyl-2-thiobarbituric acid (Inactin, Byk Gulden, Konstanz, FRG) and placed on a heated table to maintain body temperature at C. After a tracheostomy, catheters were inserted into both jugular veins for infusions, the left carotid artery and the right femoral artery for blood sampling and blood pressure monitoring, and the left ureter for urine collection. Isoncotic albumin solution (3.6 ml) and isotonic saline (1.5 ml) were given for 1 hour after surgery, followed by a 3.3 ml/hr infusion of inulin in isotonic saline for the remainder of the experiment. After initiation of infusions, the rats were prepared for in vivo microperfusion as previously described.9 In brief, the abdomen was opened with a left subcostal flank incision, and the left kidney was separated from the peritoneal fat. The kidney was then placed on a holder and bathed in mineral oil preheated at 370 C. Continuous microperfusion of superficial proximal convoluted tubules was performed with a Hampeltype perfusion pump. Early proximal convoluted tubules were identified by the intravenous injection of lissamine green solution. A micropipette (8 gm o.d.) connected to a microperfusion pump and containing dyed fluid (composition detailed below) was positioned in an early proximal convoluted tubule. Injections of small volumes of this fluid were used to identify proximal tubules having five or more surface loops distally. A glass micropipette (8,um o.d.) containing bone wax was inserted into the second loop of the identified proximal tubule. Wax was forced into the tubules by a hydraulic microdrive to obstruct the flow.10 A hole made by the perfusion pipette on the first loop allowed the glomerular filtrate to escape onto the surface of the kidney. A perfusion micropipette was then positioned in the third loop to perfuse the proximal convoluted tubules with a Ringer-like solution (Na+ 147 mm, Cl mm, K' 5 mm, HCO3-5 mm, Ca mm, Mg2+ 1 mm, HPO4-1 mm, S042-1 mm, urea 5 mm, and FD&C Blue No %; the final ph value was adjusted to 7.4). The perfusion rate of the pump was set at 35 nl/min in all the experiments. Timed complete collection of fluid reaching the last surface loop of the proximal tubule was obtained in a mineral oil-filled pipette. After the micropipette was inserted into the collection site, an oil block stained with Sudan black B was placed distal to the collection site. The rate of fluid collection was adjusted to maintain a constant position of the oil droplet and a constant luminal diameter. After completion of the microperfusion, the perfused segment was filled with latex (Canton Bio-Medical Products, Boulder, Colorado) to determine its length by microdissection.11 To validate the methodology in regard to the use of tubule flow rate interchangeability with sodium reabsorption, the Group 1 experiment was conducted. Group 1: Effect of sodium concentration in the perfusate on tubular reabsorption by superficial proximal tubules. After 190 minutes from the start of the intravenous infusions, microperfusions of superficial proximal convoluted tubules were performed with the perfusate described in "In Vivo Microperfusion Study" to determine the tubular reabsorption of fluid. Perfusate was then changed to the low-sodium perfusate by replacing the sodium with choline (Na 7 mm, choline 140 mm, other compositions of the perfusate were not changed), and microperfusions of the same nephrons were repeated. In nine proximal convoluted tubules, the order of the experiment was reversed. The tubules were first perfused with the low-sodium perfusate and then reperfused with a normal sodium perfusate. Twenty superficial proximal convoluted tubules were perfused in this group. The effect of sodium concentration in the perfusate on tubular reabsorption by superficial proximal convoluted tubules is shown in Table 1. Since the effect of sodium concentration in the perfusate on the proximal reabsorption was not affected by the order of experiments (low-sodium perfusate first, then normal sodium, or vice versa), all microperfusion data were pooled and analyzed together. When

3 1186 Circulation Research Vol 66, No 5, May 1990 the sodium concentration was decreased to 7 mm, tubular reabsorption was remarkably decreased from to 0.4±0.2 nl/min/mm. This result confirmed the recent report of Bank et al12 and showed that the major part of the tubular reabsorption observed in our in vivo microperfusion study is sodium dependent. Furthermore, this result suggested that the tubular reabsorption of fluid measured in our experiment reflected sodium reabsorption by tubules. Experimental Protocols The experimental protocols were designed to establish the effects of altered renal perfusion pressure on superficial proximal tubular fluid reabsorption. Four additional groups of rats were studied according to the following protocols. Group 2: Effect of decreased renal perfusion pressure on tubular reabsorption by superficial proximal tubules. After the intravenous infusions were started, a Silastic pressure cuff was placed around the aorta above the renal arteries. Three hours after the initiation of infusions, the RPP was decreased by inflating the pressure cuff and was kept at the decreased level by connecting the cuff to an electronic servo-controlling system. This system allows for precise regulation of RPP (±1-2 mm Hg) by means of suprarenal aortic constriction.13 A catheter in the femoral artery was used to monitor RPP, and a catheter in the carotid artery was used to monitor mean arterial pressure. Ten minutes later, one 30-minute clearance was taken, during which the measurements of RPP, mean arterial pressure, and urine volume were made; calculations of urinary sodium excretion, GFR, and fractional excretion of sodium (FENa) were performed. During this period, microperfusions of superficial proximal convoluted tubules were also performed to determine the absolute reabsorption of fluid. After the first clearance period, the pressure cuff was deflated and the RPP was allowed to return to its basal value. Approximately 10 minutes later, a second 30-minute clearance period was taken, and the measurements and recollection microperfusions were repeated. For the reperfusion of the same proximal convoluted tubules, both the perfusion pipette and the collection pipette were placed in the tubules through the holes made during the initial perfusion period. In four rats, the order of the experiment was reversed. The RPP was allowed to remain at its normal values during the first clearance period and was then decreased during the second clearance period. Twenty-two superficial proximal convoluted tubules of seven rats were perfused in this group. Group 3: Time control study for decreased renal perfusion pressure. Although a Silastic pressure cuff was placed around the aorta above the renal arteries, it was kept deflated throughout the experimental period. The remainder of the experimental protocol was the same as for Group 2. Twenty-six superficial proximal convoluted tubules of seven rats were perfused in this group. Group 4: Effect of increased renal perfusion pressure on tubular reabsorption by superficial proximal tubules. Silk ligatures were loosely placed around the celiac and mesenteric arteries and the aorta caudal to the renal arteries. After 190 minutes from the initiation of infusions, one 30-minute control clearance was taken. Both mean arterial pressure and RPP were monitored through a catheter in the carotid artery in this group. During this control period, microperfusions were done to determine the absolute reabsorption of fluid by superficial proximal convoluted tubules at the normal RPP. After the control clearance period, the celiac and mesenteric arteries and the aorta caudal to the renal arteries were occluded by tightening the silk ligatures placed around these arteries. This method was reported to increase the RPP by increasing the peripheral vascular resistance.514 Ten minutes after the RPP was elevated, a second 30-minute clearance period was taken, and the measurements and recollection microperfusions were repeated. Thirty-six superficial proximal tubules of nine rats were used in this group. Group 5: Effect of increased mean arterial pressure with nornal renal perfusion pressure on tubular reabsorption by superficial proximal tubules. To determine whether the occlusion of celiac and mesenteric arteries and the infrarenal aorta influences superficial proximal reabsorption and urinary sodium excretion without elevating RPP, RPP was controlled at the normal level by suprarenal aortic constriction throughout the experimental period. Instead of the femoral artery catheter, a catheter was inserted into the aorta up to the orifice of the left renal artery through the iliac artery to monitor the RPP in this group. Silk ligatures were loosely placed around the celiac and mesenteric arteries and the aorta caudal to the left renal artery. In addition, a Silastic cuff was placed around the aorta cephalad to the renal arteries. During the second 30-minute clearance period, the mean arterial pressure was elevated by occluding the celiac and mesenteric arteries and the aorta caudal to the renal arteries. However, RPP was kept constant at the basal level by inflating the servocontrolled pressure cuff placed around the suprarenal aorta. The remainder of the experimental protocol was the same as for Group 4. Twenty-nine superficial proximal convoluted tubules of eight rats were used in this group. Analysis Inulin concentrations in plasma and urine were determined by the anthrone method.15 Sodium concentrations were measured with a Beckman E-2A electrolyte analyzer (Beckman Instruments, Fullerton, California). The volumes of collected tubule fluid were measured with 1-1l constant bore capillaries. The length of latex casts of the perfused proximal tubule segments was determined by planimetry. Proximal convoluted tubule reabsorption was calculated by dividing the balance of tubular perfusion rate and tubular flow rate at the collection site by the length of

4 TABLE 2. Kinoshita and Knox Renal Perfusion Pressure and Proximal Tubules 1187 Effect of Renal Perfusion Pressure on Urinary Sodium Excretion From Left Kidneys RPP MAP V UNaV GFR FENa (mm Hg) (mm Hg) (gl/min) (.teq/min) (ml/min) () Group 2 (decreased RPP) (n=7) Low RPP 99+3* 133± * 0.71±0.16* t 0.45±0.11* Normal RPP 125±6 128±7 16.9± ± ± ±0.23 Group 3 (time control) (n=7) Normal RPP 121±2 126±3 13.7± ± ± ±0.25 Normal RPP 121±2 127±2 13.6± ± ± ±0.21 Group 4 (increased RPP) (n=9) Normal RPP 126±4 126±4 17.7± ± ± ±0.24 High RPP 149±4* 149±4* 27.4± ±0.85t 1.34± t Group 5 (increased MAP with normal RPP) (n=8) Normal RPP 132±2 135±4 14.5± ± ± ±0.34 Normal RPP 132±2 158±3* 13.0± ± ± ±0.33 RPP, renal perfusion pressure; MAP, mean arterial pressure; V, urine flow from left kidneys; UNaV, absolute sodium excretion from left kidneys; GFR, glomerular filtration rate of left kidneys; FENa, fractional excretion of sodium in urine; n, number of rats used. *p<0.01, significantly different from values in normal RPP. tp<0.05, significantly different from values in normal RPP. the perfused tubule segment. All values are expressed as mean-+±sem. Comparisons were made by paired t tests. A value of p<0.05 was considered statistically significant. Results The effects of altered RPP on urine volume, urinary sodium excretion, GFR, FENa, and tubular reabsorption by the superficial proximal convoluted tubules are shown in Tables 2 and 3. In Group 2, the responses of GFR, urinary sodium excretion, and proximal tubular reabsorption to the decreased RPP were not influenced by the order of the experiments (low RPP first, then normal RPP, or vice versa). Therefore, the data were pooled and analyzed together. When the RPP was decreased from to 99±3 mm Hg by suprarenal aortic constriction, urine volume, urinary sodium excretion, and FENa TABLE 3. were decreased significantly. However, neither tubular flow rate at the late proximal collection sites nor tubular reabsorption by the superficial proximal tubules was altered by this decrease of RPP. Tubular reabsorption at the normal RPP was 4.4±0.5 nl/ min/mm and that at the decreased RPP was nl/min/mm (n=22). When the RPP was not changed (from 121±2 to 121±2 mm Hg), urine volume, urinary sodium excretion, FENa, and superficial proximal reabsorption were not changed. When the RPP was elevated from 126±4 to 149 ±4 mm Hg by tying the mesenteric and celiac arteries and the infrarenal aorta, urinary sodium excretion and FENa were increased significantly. Tubular flow rate at the collection sites was increased and tubular reabsorption by the superficial proximal tubules was depressed remarkably by this elevation of RPP (from 4.1±0.3 nl/min/mm at 126±4 mm Hg to 2.5 ±0.3 Effect of Renal Perfusion Pressure on Tubular Reabsorption by Superficial Proximal Convoluted Tubules Length of Tubular flow rate of Absolute perfused tubules collection sites reabsorption RPP (mm Hg) (mm) (nl/min) (nl/min/mm) Group 2 (decreased RPP) (n=22) Low RPP 99+3* 3.5+± ± Normal RPP 125± ±0.5 Group 3 (time control) (n=26) Normal RPP 121±2 3.0± ± ±0.3 Normal RPP 121±2 3.0± ± ±0.4 Group 4 (increased RPP) (n=36) Normal RPP 126±4 3.7± ± ±0.3 High RPP 149±4* 3.7± ±0.6* 2.5±0.3* Group 5 (increased MAP with normal RPP) (n=29) Normal RPP 132±2 3.4± ± ±0.4 Normal RPP 132±2 3.4± ± ±0.4 RPP, renal perfusion pressure; n, number of perfused superficial proximal convoluted tubules; MAP, mean arterial pressure. *p<0.01, significantly different from values in normal RPP.

5 1188 Circulation Research Vol 66, No 5, May 1990 t I z W LJL h _ 0 * Decreased R.P.P. RnA Normal R.P.P RPP (mm Hg) 9 1.,.- IT 1 Increased R.P.P a) 30 (0 c0 Ua) 25 C CO a) cc Cu 15, 10 C,),0 I.- E 0-0~ a) 0 CL 0 a U m. c 1- FIGURE 1. Graph showing effect of renal perfusion pressure (RPP) on fractional excretion of sodium in urine (FENa) and tubularflow rate at collection sites of microperfused superficial proximal convoluted tubules. Proximal tubules were perfused with Ringer-like solution at a rate of 35 nl/min. RPP was decreased by suprarenal aortic constriction and was increased by increasing total peripheral vascular resistance. Vertical and horizontal lines represent SEM. *p<0.01 and tp<0.05, significantly different from the values in normal RPP. nl/min/mm at mm Hg, n=36, p<0.01). When the RPP was controlled at normal values by suprarenal aortic constriction and occlusion of the celiac and mesenteric arteries and the aorta caudal to the renal arteries, the urinary sodium excretion, FENa, and superficial proximal tubular reabsorption (from 3.6±0.4 nl/min/mm at 132±2 mm Hg to 3.9±0.4 nl/min/mm at 132±2 mm Hg, n=29) did not change. Discussion The results of these experiments demonstrate that a 26±3 mm Hg decrease of RPP did not augment the superficial proximal reabsorption, which coincides with our previous observation with free-flow micropuncture of superficial proximal tubules.6 On the other hand, when the RPP was elevated by 24±2 mm Hg, the rate of proximal tubular reabsorption was decreased from 4.1±0.3 to 2.5±0.3 nl/min/mm (13.2±0.7 to 8.0±0.6 nl/min, Figure 1). This change is very similar to the changes of superficial proximal reabsorption found by Chou and Marsh4 (13.4 ± 1.7 to 6.6±1.1 nl/min) when they increased the RPP by 23 mm Hg and perfused the superficial proximal convoluted tubules with artificial glomerular filtrate. These data indicate that, in rats, superficial proximal reabsorption is affected and decreased only when RPP is increased above normal levels. Pressure natriuresis is a phenomenon during which the urinary sodium excretion is positively influenced by acute changes in RPP both above and below normal pressures.1 The contribution of proximal tubules to this phenomenon was implied both by a lithium clearance study and by a study using diuretics to block distal nephron sodium reabsorption.2,3 These findings, coupled with the micropuncture study demonstrating increases in proximal reabsorption in deep but not superficial nephrons in response to decreases in RPP,6 suggest that there may be a heterogeneity in responses between superficial and deep nephrons. In the dog, on the other hand, the majority of micropuncture studies have failed to detect the change of sodium reabsorption by the superficial proximal tubules, even if RPP is elevated above normal levels These different responses of dog and rat superficial sodium reabsorption to an increased RPP might be the result of species differences of proximal tubular functions. Alternatively, local renal decapsulation performed only in dog micropuncture studies may attenuate the response of proximal sodium reabsorption to an elevated RPP. Therefore, the proximal tubules under investigation are exposed to an abnormally low renal interstitial hydrostatic pressure. It has been demonstrated that increases in RPP elevate renal interstitial hydrostatic pressure.19,20 This rise in interstitial hydrostatic pressure is an important link between the RPP and the reabsorption by the proximal tubules.2' Because decapsulation of the kidney attenuates the rise of renal interstitial hydrostatic pressure in response to elevations of RPP,20,22 the interstitial hydrostatic pressure-mediated changes of proximal tubular reabsorption may be attenuated in the dog micropuncture studies. Although the mechanism responsible for the different responses of superficial proximal sodium reabsorption to the increased and decreased RPP is unclear, backflux through the proximal tubules is a possible hypothesis to explain the elevated RPPinduced inhibition of proximal sodium reabsorption. Boulpaep and coworkers23,24 showed that the backflux of sodium through the tight junctions of tubular cells is responsible for the reduced sodium reabsorption by the proximal tubules in response to plasma volume expansion. They proposed that increased renal interstitial hydrostatic pressure was one of the possible factors that causes backflux.23 It has been

6 Kinoshita and Knox known that there is a parallel change between the renal interstitial hydrostatic pressure and the RPP.19,20,25 Therefore, this thesis may explain the decreased rate of proximal reabsorption in response to elevated RPP. However, the lack of response of proximal reabsorption to the decreased RPP cannot be explained by this theory. Furthermore, recent studies in our laboratory2126 showed that the elevated renal interstitial hydrostatic pressure caused by renal interstitial volume expansion inhibited proximal sodium reabsorption, and this inhibition could be blocked by prostaglandin synthesis inhibitors. This result suggests that simple backflux through the proximal tubules is not the major mechanism of the elevated renal interstitial hydrostatic pressureinduced inhibition of proximal sodium reabsorption. The response of mediators such as the reninangiotensin and prostaglandin systems, which link RPP and superficial proximal sodium reabsorption, might account for the different responses of this nephron segment to the increased and decreased RPP. The relative production of such mediators may be changed differentially when the RPP is elevated as compared with decreases in RPP. Although further studies are necessary to elucidate the mechanism of RPP-induced changes of superficial proximal reabsorption, the present study clarified the different responsiveness of superficial proximal reabsorption to decreased and to increased RPP. Acknowledgments The authors thank Marcy Onsgard for technical assistance, June M. Hanke for secretarial assistance, and J. Michael Gonzalez-Campoy for composing the figure. References 1. Romero JC, Knox FG: Mechanisms underlying pressurerelated natriuresis: The role of the renin-angiotensin and prostaglandin systems. Hypertension 1988;11: Kleinman LI, Banks RO: Pressure natriuresis during saline expansion in newborn and adult dogs. Am J Physiol 1984; 246:F828-F Haas JA, Granger JP, Knox FG: Effect of meclofenamate on lithium excretion in response to changes in renal perfusion pressure. J Lab Clin Med 1988;111: Chou CL, Marsh DJ: Role of proximal convoluted tubule in pressure diuresis in the rat. Am JPhysiol 1986;251:F283-F Chou CL, Marsh DJ: Time course of proximal tubule response to acute arterial hypertension in the rat. Am J Physiol 1988; 254:F601-F Haas JA, Granger JP, Knox FG: Effect of renal perfusion pressure on sodium reabsorption from proximal tubules of superficial and deep nephrons. Am J Physiol 1986;250: F425-F429 Renal Perfusion Pressure and Proximal Tubules Roman RJ: Pressure-diuresis in volume-expanded rats: Tubular reabsorption in superficial and deep nephrons. Hypertension 1988;12: Liebau G, Levine DZ, Thurau K: Micropuncture study on the dog kidney: I. The response of the proximal tubule to changes in systemic blood pressure within and below the autoregulatory range. Pflugers Arch 1968;304: Greger RF, Lang FG, Knox FG, Lechene CP: Absence of significant secretory flux of phosphate in the proximal convoluted tubule. Am J Physiol 1977;232:F235-F Gutsche HU, Muller-Suur R, Hegel U, Hierholzer K, Luderitz S: A new method for intratubular blockade in micropuncture experiments. Pflugers Arch 1975;334: Cortell S: Silicone rubber for renal tubular injection. J Appl Physiol 1969;26: Bank N, Aynedjian HS, Muty BF: Proximal bicarbonate absorption independent of Na'-HW exchange: Effect of bicarbonate load. Am J Physiol 1989;256:F577-F Hester RL, Granger JP, Williams J, Hall JE: Acute and chronic servo-control of renal perfusion pressure. Am J Physiol 1983;244:F455-F Roman RJ, Cowley AW Jr: Characterization of a new model for the study of pressure-natriuresis in the rat. Am J Physiol 1985;248:F190-F Fuhr J, Kaczmarczyk J, Kruttgen CD: Eine einfache colorimetrische Methode zur Inulinbestimmung fur Nierenclearanceuntersuchungen bei Stoffwechsolgesunden und Diabetikern. Klin Wochenschr 1955;33: DiBona GF, Kaloyanides GJ, Bastron RD: Effect of increased perfusion pressure on proximal tubular reabsorption in the isolated kidney. Proc Soc Exp Biol Med 1973;143: Navar LG, Bell PD, Burke JJ: Autoregulatory responses of superficial nephrons and their association with sodium excretion during arterial pressure alterations in the dog. Circ Res 1977;41: Dresser RP, Lynch RE, Schneider EG, Knox FG: Effect of increases in blood pressure on pressure and reabsorption in the proximal tubule. Am J Physiol 1971;220: Khraibi AA, Haas JA, Knox FG: Effect of renal perfusion pressure on renal interstitial hydrostatic pressure in rats. Am J Physiol 1989;256:F165-F Garcia-Estafi J, Roman RJ: Role of renal interstitial hydrostatic pressure in the pressure diuresis response. Am Physiol 1989;256:F63-F Haas JA, Granger JP, Knox FG: Effect of intrarenal volume expansion on proximal sodium reabsorption. Am J Physiol 1988;255:F1178-F Khraibi AA, Knox FG: Effect of renal decapsulation on renal interstitial hydrostatic pressure and natriuresis. Am J Physiol 1989;257:R44-R Boulpaep EL: Permeability changes of the proximal tubule of Necturus during saline loading. Am JPhysiol 1972;222: Sackin H, Boulpaep EL: Models of coupling of salt and water transport, proximal tubular reabsorption in Necturus kidney. J Gen Physiol 1979;66: Roman RJ, Cowley AW Jr, Garcia-Estafil J, Lombard JH: Pressure-diuresis in volume-expanded rats: Cortical and medullary hemodynamics. Hypertension 1988;12: Kinoshita Y, Knox FG: Role of prostaglandins in proximal tubule sodium reabsorption: Response to elevated renal interstitial hydrostatic pressure. Circ Res 1989;64: KEY WORDS * kidney * urine * sodium * proximal tubule