Nephron Glomerular Filtration Rate Research Articles

Influence of water-diuresis or saline volume expansion on deep nephron tubuloglomerular feedback.

We have recently demonstrated the existence of a tubuloglomerular feedback mechanism in juxtamedullary nephrons in rat kidneys during antidiuresis. In the present experiments, we have investigated the influence of water-diuresis on Munich Wistar rats and in homozygote Brattleboro rats. We have also observed the effect of saline volume expansion on the tubuloglomerular feedback of juxtamedullary nephrons in Munich Wistar rats. For comparison, the feedback mechanism was also studied in surface nephrons during water-diuresis in Munich Wistar rats. Measurements of flow rate in the descending limb of Henle and single nephron glomerular filtration rate (GFR) using micropuncture at the renal papilla were performed, while the ascending limb was microperfused at varying perfusion rates with a modified Ringer solution. In surface nephrons early proximal flow rate, single nephron GFR and stop-flow pressure was measured during microperfusion of the end-proximal loop. No significant changes were measured in surface nephrons during water-diuresis: the tubular flow rates, feedback responses, stop-flow pressure and stop-flow pressure changes were similar to those during anti-diuresis. In juxtamedullary nephrons, Henle loop flow rate increases during water-diuresis but the feedback-mediated flow and single nephron GFR response curves obtained during microperfusion were unaltered compared to controls. Together, these results indicate that the feedback could be more activated during water-diuresis than during control conditions. On the other hand, during saline volume expansion, reduced tubuloglomerular feedback sensitivity was found as shown earlier for surface nephrons. The reduction of tubuloglomerular feedback sensitivity therefore seems to be important in maintaining salt-, but not water-balance.

Single nephron hyperfiltration and proteinuria in a newly selected rat strain with superficial glomeruli.

Alterations in glomerular permeability were studied in female MWF/Ztm rats, newly selected from the Munich Wistar rats with a high number of superficial glomeruli. This strain is characterized by a diminished number of functioning nephrons, an elevated arterial blood pressure and a high proteinuria averaging 24 mg/24 h. Samples of Bowman capsular space (BCS) obtained by free-flow renal micropuncture techniques with pressure control were analyzed for albumin and high-molecular-weight (HMW) proteins by ultramicrodisc electrophoresis. The measured mean albumin and HMW protein concentration in BCS were 1.72 g/l and 0.66 g/l, respectively. The glomerular filtration rate (GFR) averaged 0.74 ml/min/g kidney weight and the single nephron GFR (SNGFR) 48 nl/min. Ultrastructural studies revealed focal bleb-like alterations of the podocytes as has been observed in hyperfiltration states. We suggest that the reduced number of functioning nephrons in the kidneys of these rats could induce glomerular hyperfiltration and permselectivity changes, which cause a high glomerular protein leakage.

Reduced renal blood flow in early cisplatin-induced acute renal failure in the rat.

Studies were designed to determine the cause of the reduced glomerular filtration rate (GFR) in early cisplatin-induced acute renal failure. Rats were studied 72 h following a single intraperitoneal injection of cisplatin (5 mg/kg) or vehicle (0.9% NaCl). Whole kidney GFR and blood flow were lower in cisplatin-treated animals than in controls (0.30 +/- 0.06 vs. 1.17 +/- 0.06 ml X min-1 X g kidney wt-1 and 5.30 +/- 0.62 vs. 8.25 +/- 0.43 ml X min-1 X g kidney wt-1, respectively; P less than 0.001), as were superficial nephron GFR and stop-flow pressure (20.2 +/- 2.1 vs. 34.5 +/- 2.0 nl X min-1 X g kidney wt-1 and 29.0 +/- 1.9 vs. 39.8 +/- 1.3 mmHg, respectively; P less than 0.001). After volume expansion, renal plasma flow increased in control rats, whereas whole kidney and single nephron GFR did not change. In experimental animals, whole kidney filtration rate rose to 0.58 +/- 0.07 ml X min-1 X g kidney wt-1, single nephron filtration rate increased to 29.9 +/- 3.5 nl X min-1 X g kidney wt-1 (P less than 0.005), and renal plasma flow increased to 5.62 +/- 0.60 ml X min-1 X g kidney wt-1 (P less than 0.05). Intratubular hydrostatic pressure was not different in the two groups before or after volume expansion. The results of these studies show that the reduced GFR in early cisplatin-induced renal failure is due, in part, to reversible changes in renal blood flow and renal vascular resistance.

DOPAMINE REGULATION OF GLOMERULAR FILTRATION RATE AND RENAL BLOOD FLOW IN YOUNG AND ADULT RAT.THE POSSIBLE ROLE OF DA2 RECEPTORS

Dopamine (DA),widely used for treatment of acute prerenal failure (APRF),induces renal vasodilation and increase in glomerular filtration rate (GFR).The exact mechanism of DA action has not been clarified.Two types of DA receptors (1 and 2) have recently been identified.DA1 is linked to adenylate cyclase activation,while DA2 is not, and might be linked to calcium. DA1 is predominantly found in the nonglomerular renal vessels,while in the glomeruli only DA2 has been demonstrated. DA has successfully been used for treatment of APRF in preterm infants, but little is known about developmental differences in the renal response to the drug.We examined the renal hemodynamic effects of low dose (0.2 and 1.0/ug/kg/min) DA in young (Y, 24 d old) and adult (A, 60 d old) rats, and also tried to evaluate the possibility of calcium linkage and the role of the DA2 receptors by performing studies with and without verapamil (a potent calcium channel blocker,VP,20/ug/kg/min) infusions.Single nephron (SN) GFR was measured in 10 Y and in 10 A rats. In A rats 0.2 DA induced a 32% (p < 0.01) and 1.0 DA a 45% (p < 0.001) increase in SNGFR. In Y rats the increase of SNGFR was somewhat smaller, but with 1.0 DA it was statistically significant (33%,p < 0.001). In 8 adult rats the addition of VP abolished the DA induced increase in SNGFR.Blood flows (BF) were determined in 32 A rats with microsphere technique. 1.0 DA alone significantly increased renal cortical, renal medullary and mesenterial BFs. The addition of VP significantly decreased the DA induced increase of the renal cortical BF, but did not influence the DA induced vasodilation in the renal medulla and mesenterium. Conclusions: Y rats can respond to low dose DA but certain dose dependent differences might exist between Y and A rats suggesting a maturational process for DA receptors and/or effector responses. At 1.0 DA the drug induced increase of renal cortical BF is mainly modulated by calcium linked receptors,which we assume are DA2s, while in the renal medulla and mesenterium the cAMP linked DA1 plays the main regulating role.

Single nephron function during prolactin-induced pseudopregnancy in the rat.

Whole kidney and renal micropuncture techniques were used to investigate the effects of chronic prolactin treatment on kidney function in anaesthetized female rats. At the whole kidney level, glomerular filtration rate (GFR) and fluid reabsorption were both significantly (P less than 0.02) increased in the hormone-treated group. At the single nephron level, GFR and proximal fluid reabsorption were also increased (P less than 0.05) by prolactin treatment. Fractional reabsorption was also enhanced at the proximal tubular level in hormone-treated animals. Such changes in renal function are similar to those seen in rat pregnancy and cervically stimulated pseudopregnancy. Since circulating prolactin concentrations are increased in both reproductive states, the hormone may play an important role in establishing the characteristic renal changes seen therein.

Nephron responses to converting enzyme inhibition in non-clipped kidney of Goldblatt hypertensive rat at normotensive pressures

To evaluate the effects of angiotensin converting enzyme inhibition (SQ 20881, CEI) on superficial nephron function of the non-clipped kidney in Goldblatt hypertensive rats in the absence of alterations in renal arterial pressure, control renal arterial pressure (RAP) was reduced first to the range generally obtained during CEI (124 +/- 4 mm Hg). RAP was maintained during the CEI period by adjustment of a suprarenal aortic clamp. At the reduced RAP, whole kidney and single nephron glomerular filtration rates (GFR) were reduced from the hypertensive levels and were lower than the measurements in normotensive control rats. During CEI, whole kidney GFR and single nephron GFR increased by 55 and 42%, respectively. There were decreases in absolute as well as fractional proximal reabsorption rates. In the intermediate nephron segment, fractional reabsorption was decreased, but absolute fluid reabsorption increased in proportion to the increased delivery rate. Proximal tubule and peritubular capillary hydrostatic pressures increased significantly during CEI also. These results indicate that an increased activity of the renin-angiotensin system occurring in Goldblatt hypertensive rats subjected to aortic constriction exerts effects to lower GFR and increase proximal reabsorption rate. The concomitant superficial nephron and whole kidney GFR responses to CEI when arterial pressure was maintained suggests that the pre-existing levels of angiotensin exerted similar influences on the total nephron population.

Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal renal ablation.

Ablation of greater than 70% of renal mass in the rat results in hypertension, proteinuria, and glomerular sclerosis of the remnant kidney. Rats with a remnant kidney have increased excretion of thromboxane in the urine when compared with normal rats. Chronic oral administration of OKY 1581, an inhibitor of thromboxane synthesis, in rats with a remnant kidney increases renal blood flow and glomerular filtration rate (GFR), decreases protein and thromboxane excretion in the urine, lowers blood pressure and cardiac index, and improves renal histology. The degree of hypertrophy of the remnant kidney was unaffected by administration of OKY 1581. Calculated values for single nephron plasma flow and GFR were significantly greater in rats with remnant kidneys given OKY 1581 than in rats given saline. Acute i.v. administration of OKY 1581 increased renal plasma flow and GFR in rats with a remnant kidney but not in normal rats or rats with a remnant kidney previously treated with acetylsalicyclic acid. OKY 1581 markedly inhibited platelet aggregation. We suggest that in this model of renal disease platelet aggregation and intraglomerular thrombosis play a key role in the development of glomerulosclerosis. Inhibition of platelet aggregation prevents development of glomerulosclerosis, hypertension, and cardiac hypertrophy. We suggest that hyperperfusion and hyperfiltration per se occurring in remnant glomeruli are not directly responsible for the development of glomerulosclerosis.

Chronic partial ureteral obstruction in the neonatal guinea pig. II. Pressure gradients affecting glomerular filtration rate.

Neonatal guinea pigs with chronic partial ureteral obstruction (CPUO) and contralateral nephrectomy develop hydroureteronephrosis and reduced glomerular filtration rate (GFR) without significant reduction of renal blood flow. To investigate the role of pressure gradients in determination of GFR, micropuncture studies were performed in animals 23 +/- 3 days of age subjected to left ureteral constriction and right nephrectomy within the first 2 days of life and compared to uninephrectomized controls. Resulting ureteral dilatation was variable, with kidney weight and ureteral diameter being proportional to the rise in ureteral pressure (PU). In individual animals with severe CPUO (ureteral diameter greater than or equal to 3 mm), distal tubular transit time was either normal (31-90 s) or prolonged (greater than 120 s). Superficial single nephron GFR (SNGFR) was inversely correlated with PU. Glomerular capillary pressure and afferent arteriolar colloid oncotic pressure were not affected by CPUO while peritubular capillary, proximal and distal intratubular hydrostatic pressure increased as a function of PU. As a result, afferent effective filtration pressure (EFPA) was reduced in severe (10.0 +/- 1.1 mm Hg) compared to mild CPUO (13.4 +/- 0.5 mm Hg), but was not different from controls (11.3 +/- 0.9 mm Hg). For both control and CPUO groups, superficial SNGFR increased by 0.5 nl/min for each mm Hg increase in EFPA but for a given EFPA, SNGFR was 6 nl/min lower in guinea pigs with CPUO. These results indicate that higher EFPA in animals with mild compared to severe CPUO contributes to maintenance of higher SNGFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of renal arterial angiotensin I infusion on glomerular dynamics in sodium replete dogs

During intrarenal infusion of angiotensin I (AI), conversion to angiotensin II (AII) within the kidney has been shown to occur early enough to decrease glomerular filtration rate (GFR). To evaluate further the mechanism by which AI decreases GFR, micropuncture studies were conducted in sodium replete dogs. Feedback-mediated alterations in glomerular function were minimized by reducing renal arterial pressure to 90 mm Hg. During infusion of AI (0.82 +/- 0.01 micrograms min-1), renal blood flow (3.91 +/- 0.25 ml min-1 g-1) and GFR (0.63 +/- 0.04 ml min-1 g-1) decreased by 36.7 +/- 6.1% and 18.9 +/- 6.1%, respectively. Similarly, single nephron GFR decreased from 66.4 +/- 3.8 to 40.0 +/- 3.2 nl min-1 and estimated glomerular plasma flow (280 +/- 49 nl min-1) decreased by 55 +/- 6%. Stop-flow pressure (40.5 +/- 3.6 mm Hg) did not change significantly, while proximal tubular (21.8 +/- 1.4 mm Hg) and peritubular capillary pressures (13.2 +/- 1.8 mm Hg) decreased by 25.5 +/- 2.8% and 49.4% +/- 5.1%, respectively. Glomerular capillary and effective filtration pressures were not altered significantly. There were increases in both preglomerular (168%) and efferent (203%) arteriolar resistances, along with a decrease in the glomerular filtration coefficient (Kf) from 4.6 +/- 0.6 to 2.5 +/- 0.5 nl mm Hg-1 min-1. These data indicate that augmented intrarenal conversion of circulating AI reduces GFR as a consequence of decreases in Kf as well as in glomerular plasma flow, the latter being due to concomitant increases in preglomerular and efferent arteriolar resistances.

Glucocorticoid-induced inhibition of the reabsorption of inorganic phosphate in the proximal tubule in the absence of parathyroid hormone.

Previous studies from this laboratory have demonstrated a phosphaturic response to hydrocortisone. The present micropuncture studies were undertaken to localize this glucocorticoid-induced effect along the nephron. Adult female Sprague-Dawley rats were used and parathyroidectomized 3 h before the micropuncture. The animals were infused with modified Ringer solution (either without or with phosphate). Hydrocortisone increased both the end-proximal transtubular concentration gradient of inorganic phosphate, (TF/P)Pi, and the fractional delivery of Pi at the end of the proximal convolution significantly. The absolute reabsorption of Pi decreased from 95.1 +/- 29.5 (mean +/- SD) to 59.7 +/- 28.2 pmol/min (p less than 0.005) and the absolute reabsorption of Pi/single nephron glomerular filtration rate from 2.34 +/- 0.59 to 1.35 +/- 0.54 pmol/nl (p less than 0.001) during Pi-Ringer infusion. It is concluded that the glucocorticoid-induced phosphaturia is primarily a result of the inhibition of the reabsorption of Pi in the proximal tubule.

Chloride-depletion alkalosis with a normal extracellular fluid volume.

Current concepts hold that volume expansion is essential to the correction of chloride-depletion alkalosis (CDA) with chloride repletion in a permissive role. In this scheme, intranephronal fluid reabsorption would be redistributed with increased delivery to the distal nephron where the provided chloride is readily reabsorbed and the limited capacity for bicarbonate reabsorption would promote bicarbonate excretion and correction of CDA. In a model of CDA produced by peritoneal dialysis against 0.15 M NaHCO3, we have shown complete correction of CDA within 24 h without volume expansion by either oral isotonic sodium or chloride salts with 70 mM chloride and despite an obligatory bicarbonate load and negative sodium and potassium balance. During correction of CDA without volume expansion in rats by intravenous isotonic fluids containing 80 mM chloride, fractional fluid and chloride reabsorptions in the proximal convoluted tubule and in the loop segment of superficial nephrons were not different from controls but chloride reabsorption was enhanced in the collecting duct segment and probably within the distal convolution. Despite no differences in serial hematocrits, blood pressure, and measured plasma volume, kidney and nephron glomerular filtration rate (GFR) were reduced in CDA and returned to normal upon recovery 24 h later.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic alkalosis in the rat. Evidence that reduced glomerular filtration rather than enhanced tubular bicarbonate reabsorption is responsible for maintaining the alkalotic state.

Maintenance of chronic metabolic alkalosis might occur by a reduction in glomerular filtration rate (GFR) without increased bicarbonate reabsorption or, alternatively, by augmentation of bicarbonate reabsorption with a normal GFR. To differentiate these possibilities, free-flow micropuncture was performed in alkalotic Munich-Wistar rats with a glomerular ultrafiltrate total CO2 concentration of 46.5 +/- 0.9 mM (vs. 27.7 +/- 0.9 mM in controls). Alkalotic animals had a markedly reduced single nephron GFR compared with controls (27.4 +/- 1.5 vs. 51.6 +/- 1.6 nl/min) and consequently unchanged filtered load of bicarbonate. Absolute proximal bicarbonate reabsorption in alkalotic animals was similar to controls (981 +/- 49 vs. 1,081 +/- 57 pmol/min), despite a higher luminal bicarbonate concentration, contracted extracellular volume, and potassium depletion. When single nephron GFR during alkalosis was increased toward normal by isohydric volume expansion or in another group by isotonic bicarbonate loading, absolute proximal bicarbonate reabsorption was not substantially augmented and bicarbonaturia developed. To confirm that a fall in GFR occurs during metabolic alkalosis, additional clearance studies were performed. Awake rats were studied before and after induction of metabolic alkalosis associated with varying amounts of potassium and chloride depletion. In all cases, the rise in blood bicarbonate concentration was inversely proportional to a reduction in GFR; filtered bicarbonate load remained normal. In conclusion, a reduction in GFR is proposed as being critical for maintaining chronic metabolic alkalosis in the rat. Constancy of the filtered bicarbonate load allows normal rates of renal bicarbonate reabsorption to maintain the alkalotic state.

Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome.

A unilateral model of puromycin aminonucleoside (PAN)-induced albuminuria was produced in Munich-Wistar rats to examine the mechanisms responsible for renal salt retention. 2 wk after selective perfusion of left kidneys with PAN (n = 8 rats) or isotonic saline (control, n = 7 rats), increases in albumin excretion and decreases in sodium excretion were demonstrated in PAN-perfused but not in nonperfused kidneys of PAN-treated rats although systemic plasma protein concentration remained at control level. Total kidney glomerular filtration rate (GFR) and superficial single nephron (SN) GFR were also reduced selectively in PAN-perfused kidneys, on average by approximately 30%, due primarily to a marked decline in the glomerular capillary ultrafiltration coefficient (Kf), which was also confined to PAN-perfused kidneys. Values for absolute proximal reabsorption (APR) were also selectively depressed in PAN-perfused kidneys, in keeping with a similarly selective decline in peritubular capillary oncotic pressure measured in these kidneys, the latter also a consequence of the fall in Kf. In a separate group of seven PAN-treated rats, however, no differences were detected between PAN-perfused and nonperfused kidneys in the absolute amount of sodium reaching the early (0.77 +/- 0.09 neq/min vs. 0.74 +/- 0.08, P greater than 0.40) and late portions of superficial distal tubules (0.31 +/- 0.02) neq/min vs. 0.32 +/- 0.05, P greater than 0.50), despite the lesser filtered load of sodium in PAN-perfused kidneys. Suppressed sodium reabsorption in both proximal convoluted tubules and short loops of Henle of PAN-perfused kidneys contributed to this equalization of sodium delivery rates to the late distal tubule, as did comparable reabsorption along distal convolutions. In two additional groups of PAN-treated rats, infusion of saralasin (0.3 mg/kg per h, i.v.) led to substantial increases in total kidney GFR and SNGFR in PAN-perfused but not in nonperfused kidneys. Despite these increases in total and SNGFR, urinary sodium excretion by PAN-perfused kidneys remained at a level far below that for nonperfused kidneys, again indicating that the antinatriuresis characterizing the PAN-perfused kidney is due to alterations in sodium handling by the tubules rather than changes in GFR. These results therefore indicate (a) that reductions in Kf and depressed sodium reabsorption by proximal tubules and Henle's loop segments in this model are brought about by intrarenal rather than circulating or systemic factors, and (b) assuming that superficial nephrons are representative of the entire nephron population, renal salt retention in this model is due primarily to intrarenal factor(s) acting beyond the distal convolution.

Activation of the tubuloglomerular feedback mechanism in dehydrated rats.

To study the influence of the tubuloglomerular feedback control (TGF) on the regulation of glomerular filtration rate (GFR) during dehydration, micropuncture experiments were performed on surface nephrons of dehydrated rats. Dehydration was achieved by withdrawal of food and water for 24 h. The urine flow rate decreased to 1.5 microliters/min (controls 2.9 microliters/min) and GFR decreased in these rats to 0.80 ml/min (controls 1.22). TGF was studied by two different micropuncture procedures. With the first technique the changes in proximal stop-flow pressure in response to changes of the late proximal microperfusion rate were measured. With this technique the perfusion rate necessary to induce a half maximal stop-flow pressure response, the turning point, was also determined. An increased TGF sensitivity was found in dehydrated rats, as indicated by increased stop-flow pressure responses (35 versus 26%) and decreased turning points (16 versus 21 nl/min). With the second micropuncture technique the single nephron GFR (SNGFR) was measured at distal and proximal tubular sites, in the same nephron. Distal SNGFR was decreased during dehydration to 32.2 nl/min, versus 42.7 nl/min in controls. A significant difference between paired SNGFR measurements in the same nephron was observed during dehydration, the proximal value being 5.3 nl/min higher than the distal, whereas this difference was not seen in control rats. This finding indicates that activation of the feedback mechanism takes place to reduce SNGFR. It is concluded that the decrease in whole kidney GFR is partly caused by the observed increase in feedback activity. The present results are also in agreement with our earlier hypothesis that the hydrostatic and oncotic pressure conditions within the interstitial space surrounding the macula densa cells modulate the sensitivity of the tubuloglomerular feedback mechanism.

Evidence for feedback mediated reduction of glomerular filtration rate during infusion of acetazolamide.

Systemic administration of acetazolamide (ACZ) causes glomerular filtration rate (GFR) to fall. Clearance and micropuncture experiments were done to define the mechanism of this drug effect. When rats were infused with ACZ intravenously, kidney GFR fell by 30% and single nephron (SN) GFR (measured by collecting distal tubule fluid) fell by 23%. Changes in arterial blood pressure, arterial pH, extracellular fluid volume, and proximal tubule pressure were not sufficient to account for the decrease in GFR. When SNGFR was measured by collecting proximal tubule fluid, with the loop of Henle having been blocked for 2-5 min, SNGFR was higher than the distally measured value and was not different than control. The results are consistent with the fall in GFR being caused by activation of the tubulo-glomerular feedback mechanism.

Influence of bradykinin and papaverine on renal and glomerular hemodynamics in dogs.

Although it is recognized that vasodilator-induced increases in renal plasma flow are not associated with increases in glomerular filtration rate (GFR), the mechanism responsible for the failure of GFR to exhibit plasma flow dependency under these circumstances remains uncertain. To evaluate this problem further, the effects of intra-arterial infusion of two vasodilators, bradykinin (n = 7) and papaverine (n = 6), on renal hemodynamics and glomerular function of dogs were determined. Both agents increased renal blood flow; however, GFR and single nephron GFR (SNGFR) remained unchanged during bradykinin infusion and decreased significantly during papaverine infusion. Transglomerular hydrostatic pressure and mean effective filtration pressure were not altered during bradykinin infusion but were significantly reduced by papaverine. Neither agent altered the glomerular filtration coefficient. These observations indicate that, in the dog, the GFR responses during renal vasodilation are dependent primarily on the effective filtration pressure.

Influence of converting enzyme inhibition on renal hemodynamics and glomerular dynamics in sodium-restricted dogs.

Clearance and micropuncture experiments were performed to evaluate the influence of converting enzyme inhibition (CEI) (SQ 14,225) on renal hemodynamics, glomerular filtration rate (GFR), segmental vascular resistances, and superficial nephron function in anesthetized sodium restricted dogs. In one series (n = 8), renal blood flow (RBF) and GFR exhibited a high degree of autoregulatory efficiency when renal arterial pressure (RAP) was reduced from 126 +/- 5 to 86 +/- 1 mm Hg. With RAP maintained at the reduced level, CEI elicited increases in RBF (3.9 +/- 0.3 to 5.8 +/- 0.5 ml/min per g kw) and GFR (0.81 +/- 0.03 to 0.94 +/- 0.04 ml/min per g kw). With return of RAP to spontaneous levels during continued CEI, RBF and GFR autoregulatory efficiency was maintained, and was similar to that observed in control dogs subjected to the same procedures (n = 5). In the micropuncture experiments (n = 12), RAP was maintained at the reduced level (87.5 +/- .9 mm Hg), and measurements were made before and during CEI. Proximal tubule pressure, peritubular capillary pressure, stop flow pressure, and single nephron GFR (SNGFR) increased significantly. Regression analysis suggested that the increases in SNGFR were associated with small increases in the filtration coefficient. CEI reduced preglomerular resistance by 29% to 35% and efferent arteriolar resistance by 24% to 32%. These results indicate that the increased activity of the renin-angiotensin system that occurs during salt restriction exerts approximately equivalent vasoconstrictor influences on both preglomerular and postglomerular vascular resistance elements.

Functional compensatory changes after unilateral nephrectomy in rats. General and intrarenal hemodynamic alterations.

Cardiac output (CO), total peripheral resistance (TPR), renal blood flow (RBF), renal vascular resistance (RVR) and intrarenal blood flow distribution have been measured 48 h after unilateral (right) nephrectomy (UNX) and in sham-operated rats (SO). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined using standard inulin and PAH clearances. Superficial single nephron GFR (SNGFR) was measured by free-flow micropuncture techniques. Extracellular fluid volume (ECV) and plasma volume (PV) were also determined. UNX rats showed increases of 17.4% in remnant kidney GFR and 34.5% in RPF. Filtration fraction was decreased to 0.27 +/- 0.01 (control value 0.31 +/- 0.01; p less than 0.0025). SNGFR was 45% higher in UNX rats and the ratio SNGFR/GFR increased by 28%. Cardiac output also increased (33.6 +/- 1.0 for UNX rats; 28.0 +/- 1.2 ml/min/100 g BW for SO rats; p less than 0.0025) accompanied by a corresponding fall (20%) in TPR. Left kidney RBF increased by 22%, whereas RVR decreased by 21%. Blood flow through individual glomeruli increased in the outer and inner cortex and was unchanged in the midcortex. In conclusion, 48 h after unilateral nephrectomy, rats showed a hyperdynamic circulatory state with increased CO and decreased TPR; this could be involved in the acute adaptive functional and renal changes reported after uninephrectomy.

Dependency of proximal tubular fluid transport on the load of glomerular filtrate

In hydropenic rats, the reabsorption of glomerular filtrate by the proximal convoluted tubules was measured before and after reduction of its intratubular flow rate. Three different protocols were used. (1) In 26 tubules (14 rats), nephron glomerular filtration rate (SNGFR) was varied from 37.2 +/- 7.3 to 20.4 +/- 7.1 nl/min by microperfusing their loops of Henle at 0 to 5 nl/min and 40 nl/min, respectively. This 43% reduction of SNGFR was followed by a 36.0 +/- 23.3% reduction of volume reabsorption rate (P less than 0.001). Between both parameters a linear regression line can be calculated, which is given by y = 0.92 chi + 0.0017. (2) In 17 tubules (14 rats), SNGFR was altered again by feedback from 46.0 +/- 9.7 to 28.8 +/- 9.3 nl/min. The volume resorption from the first half of the proximal convoluted tubule was compared with the reabsorption in its late proximal segments, which were microperfused with proximal tubular fluid at a rate of 20 nl/min. The 36.8% reduction of SNGFR was followed by only a 28.2% reduction of volume reabsorption rate in the first half of the tubule. In the microperfused segments, however, reabsorption remained unaltered. (3) In 29 tubules (21 rats), at the midpoint of proximal convolutions, some of the tubule fluid was removed by a suction pump, and volume reabsorption rate in the late segments was compared with that in the early parts of this tubule, when SNGFR remained stable. The reduction of intratubular flow from 27.7 +/- 8.5 to 14.7 +/- 5.8 nl/min, which is 53% of control, were followed by a reduction of volume reabsorption rate in the late segment to 60.6% control. Between both parameters a regression line was calculated, which is given by y = 0.76 chi +/- 0.01. We conclude that the rate of volume reabsorption by the proximal tubule depends on its intratubular load of glomerular filtrate and, further, that this dependency accounts predominantly for the maintenance of glomerular tubular balance under conditions of hydropenia.

Glomerular adaptations to chronic dietary salt restriction or excess.

Micropuncture studies were performed in 33 Munich-Wistar rats maintained chronically either on dietary NaCl restriction (group 1) or excess (group 2). Values for single nephron (SN) and total kidney glomerular filtration rate (GFR) were identical in both groups. Nevertheless, because of preferential efferent vasoconstriction, glomerular capillary hydraulic pressure (PGC) was higher in group 1, offsetting the lower initial glomerular plasma flow rate (QA) also found in group 1. The pressor response to infusion of exogenous angiotensin II (AII) was less in group 1 than in group 2, suggesting that vascular receptors for AII may have been occupied by endogenous hormone, the latter leading to the efferent arteriolar vasoconstriction. In addition to AII, prostaglandins also appear to be involved in the adaptations of the glomerular microcirculation to chronic variations in salt intake. In group 1, indomethacin or meclofenamate infusion mimicked exogenous AII, causing declines in QA and SNGFR. These changes were lacking in group 2. Because of relative contraction of plasma volume, the vasodilatory effects of prostaglandins appear to be needed in low salt animals to sustain SNGFR and QA. In the high salt group, however, since plasma volume is not contracted, maintenance of SNGFR and QA appears to be less critically dependent on endogenous prostaglandins.