Bryan J. Tucker

Angiotensin II effects upon the glomerular microcirculation and ultrafiltration coefficient of the rat.

The effects of both synthetic and biologically produced angiotensin II (AII) upon the process of glolerular filtration were examined in the plasma-expanded (2.5% body wt) Munich-Wistar rat, by micropuncture evaluation of pressures, nephron plasma flow (rpf) and filtration rate (sngfr). Plasma expansion was chosen as a control condition because (a) response to AII was uniform and predictable, (b) endogenous generation of AII was presumably suppressed, and (c) the high control values for rpf permitted accurate determination of values for the glomerular permeability coefficient (LpA) before and during AII infusion. With subpressor quantities of synthetic Asn-1, Val-5 AII (less than 5 ng/100 g body wt/min), sngfr fell from 47.7 in the control group to 39.8 nl/min/g kidney (P less than 0.005). The rpf fell to 60% of control values (P less than 0.001). Measurement of glomerular capillary (PG) and Bowmans space (Pt) hydrostatic pressures in surface glomeruli with a servo-nulling device permitted evaluation of the hydrostatic pressure gradient (deltaP = PG - Pi). DeltaP increased from 38.1 +/- 1.2 in control to 45.9 +/- 1.3 mm Hg after Asn-1, Val-5 AII and essentially neutralized the effect of decreased rpf in sngfr. The sngfr then fell as a result of a decreased in LpA from 0.063 +/- 0.008 in control to 0.028 +/- 0.004 nl/s/g kidney/mm Hg after Asn-1, Val-5 AII (P less than 0.02). Lower doses of Asp-1, Ile-5 AII (less than 3 ng/100 g body wt/min) had no effect on sngfr, rpf, deltaP, and afferent and efferent vascular resistance, but significantly elevated systemic blood pressure, suggesting peripheral effects on smooth muscle at this low dose. LpA was 0.044 +/- 0.007 nl/s/g kidney/mm Hg after low-dose Asp-1, Ile-5 AII, and 0.063 +/- 0.008 in the control group (0.02 greater than P greater than 0.1). Higher, equally pressor doses of native AII (5 ng/100 g body wt/min) produced effects almost identical to similar quantites of synthetic Asn-1, Val-5 AII upon rpf, deltaP, sngfr, and renal vascular resistance. LpA again fell to 0.026 +/- 0.004 nl/s/g kidney/mn Hg, a value almost identical to that after the synthetic AII. Paired studies with Asp-1, Ile-5 AII also demonstrated a consistent reduction in LpA.

Glomerular Hemodynamics in Rats with Chronic Sodium Depletion: EFFECT OF SARALASIN

In chronic sodium depletion the glomerular filtration rate may be reduced, and alterations in proximal tubular function may contribute to the maintenance of antinatriuresis. Measurements were made by micropuncture technique in superficial nephrons of the Munich-Wistar rat of (a) the determinants of glomerular filtration rate, (b) peritubular capillary hydrostatic and oncotic pressure, and (c) proximal tubular fractional and absolute reabsorption in both a control group (group 1, n = 12) and a group of chronically sodium-depleted rats (group 2, n = 12). Single nephron filtration rate (sngfr) was 37.2+/-1.2 in group 1 and 31.6+/-1.0 nl/min/g kidney wt (P < 0.05) in group 2. Of the factors potentially responsible for the observed reduction in sngfr, there was no change in systemic oncotic pressure or the transglomerular hydrostatic pressure gradient. Sngfr was lower in group 2 because of both a reduced single nephron plasma flow (rpf) (128+/-6 vs. 112+/-5 nl/min per g kidney wt, P < 0.05) and additionally to a decrease in the glomerular permeability coefficient, L(p)A, from a minimum value of 0.105+/-0.012 in group 1 to 0.054+/-0.01 nl/s per g kidney wt per mm Hg (P < 0.01) after chronic sodium depletion. There was no difference in fractional proximal tubular reabsorption between group 1 and group 2. Absolute proximal reabsorption (APR) was reduced from 20.8+/-1.3 in group 1 to 16.3+/-0.9 nl/min per g kidney wt in group 2. The role of angiotensin II (AII) in maintaining glomerular and proximal tubular adaptations to chronic sodium depletion was assessed in subsets of groups 1 and 2 by the infusion of the AII antagonist Saralasin at a rate of 1 mug/kg per min. In group 1 rats, Saralasin had no effect on sngfr, rpf, or L(p)A, because animals remained at filtration pressure equilibrium. In group 2 rats, AII blockade was associated with an increase in sngfr from 31.6+/-1.0 to 37.1+/-1.7 nl/min per g kidney wt (P < 0.01). Rpf increased during Saralasin infusion solely as a result of a decrease in afferent arteriolar resistance from 21.7+/-2.3 to 15.2+/-2.3 10(9) dyn-s-cm(-5) (P < 0.01). Saralasin infusion did not affect the reduced L(p)A in group 2, as L(p)A remained 0.056+/-0.02 nl/s per g kidney wt per mm Hg and rats remained disequilibrated. In spite of the increase in sngfr in group 2, AII antagonism further decreased APR to 13.1+/-1.5 (P < 0.01). Distal delivery therefore, increased from a control value of 15.3+/-1.3 to 24.3+/-1.5 nl/min per g kidney wt (P < 0.01). In conclusion, both a decrease in L(p)A and a reduction in rpf were major factors mediating the decrease in glomerular filtration rate observed in chronic sodium depletion. Saralasin infusion revealed a significant effect of AII on rpf and afferent arteriolar resistance in chronic sodium depletion, but no effect of AII on either efferent arteriolar resistance or the decrease in L(p)A could be demonstrated. Saralasin had no effect in rats that were not chronically sodium depleted. In group 2 rats AII antagonism reduced APR even though sngfr increased, suggesting an influence of AII on proximal reabsorption. The marked changes observed during Saralasin infusion in the chronically sodium-depleted rat reveal important modifying effects of endogenously generated AII on both the glomerulus and proximal tubule.

Glomerular filtration response to elevated ureteral pressure in both the hydropenic and the plasma-expanded rat.

The factors affecting glomerular ultrafiltration with elevated ureteral pressure were examined in both plasma-expanded (2.5% body weight) and hydropenic Munich-Wistar rats. Elevated ureteral pressure (20 mm Hg) alternated as the initial condition in both groups. Glomerular capillary hydrostatic pressure (PG) and Bowmans space pressure (P,) were measured directly in surface glomeruli with a servonulling device (AP - PG - Pt) systemic (πA) and efferent (πE) peritubular capillary oncotic pressures were estimated by microprotein methods, and single-nephron glomerular filtration rates (sngfr) were determined by micropuncture techniques under control ureteral pressure and after increased ureteral pressure in both experimental groups. All data were then applied to equations describing the process of glomerular ultrafiltration to define the profile of effective filtration pressure (EFP = ΔP - π) and the glomerular permeability coefficient (LpA), where sngfr = LpA EFP. In plasma-expanded rats, sngfr fell from 44.8 ± 2.2 to 38.5 ±1.5 nliters/min g−1 kidney weight (P < 0.025) with elevated ureteral pressure entirely as a result of a decrease in the hydrostatic pressure gradient (ΔP), since PG did not rise and nephron plasma flow remained constant. In hydropenic rats, sngfr fell from 34.7 ± 1.6 to 27.3 ± 1.6 nliters/min g−1 kidney weight with increased ureteral pressure. PG rose 8.7 mm Hg (P < 0.001) due to an increase in vascular resistance between the peritubular capillaries and the renal vein which prevented the reduction in ΔP. The reduction in sngfr appeared to result from a reduction in LP A resulting in disequilibration of EFP. Nephron plasma flow was not changed. The filtration response to elevated ureteral pressure was modified by the prior state of volume expansion and was not associated with changes in either nephron blood flow or afferent arteriolar resistance.

Normal transcapillary pressures in human skeletal muscle and subcutaneous tissues.

Abstract Starling pressures (capillary blood pressure, interstitial fluid pressure, blood oncotic pressure, and interstitial fluid oncotic pressure) were measured in skeletal muscle and subcutaneous tissues of 19 normal humans. Due to inaccessibility of muscle and subcutis capillaries to micropuncture, continuous recording of capillary blood pressure was confined to the fingernail-fold microcirculation. Interstitial fluid pressure was determined acutely by using wick catheters introduced under local anesthesia into tissues of the leg. Oncotic pressure of venous blood was measured in 0.1-ml samples of serum by a colloid osmometer. Interstitial fluid was collected by empty wick catheters. An equation for calculation of interstitial fluid oncotic pressure was formulated which incorporates experimentally measured values of total protein and albumin concentrations. Calculated values for interstitial fluid oncotic pressure correlated well with directly measured values. In fingernail-fold tissue of one human subject mean capillary blood pressure (± SD) was 31 ± 11 mm Hg. In leg subcutaneous tissue of the same subject, interstitial fluid pressure was −1.3 ± 0.5 mm Hg, blood oncotic pressure was 28 ± 0.6 mm Hg, and interstitial fluid oncotic pressure was 9.1 ± 1.0 mm Hg. In skeletal muscle of the same subjects leg, interstitial fluid pressure was 0.5 ± 1.5 mm Hg, and interstitial fluid oncotic pressure was 8.3 ± 1.6 mm Hg. Based on data for interstitial fluid pressure, blood oncotic pressure, and interstitial fluid oncotic pressure, and assuming the capillary membrane reflection coefficient is 0.9 for both tissues, filtration equilibrium across the capillary wall would occur at a mean capillary blood pressure of 16 mm Hg in subcutis and 18 mm Hg in skeletal muscle.

Studies on the mechanism of reduction in glomerular filtration rate after benzolamide

In previous studies, we have shown that benzolamide, a carbonic anhydrase inhibitor with diuretic activity confined primarily to the proximal tubule, causes a significant reduction in nephron filtration rate by increasing afferent and efferent arteriolar vascular resistance [30], possibly through an activation of tubuloglomerular feedback mechanism. The present studies were designed to determine if infusion of 1-sar, 8-ala angiotensin II, an angiotensin II receptor antagonist (AIIA) could prevent and reverse the vasoconstriction and resulting reduction in SNGFR with benzolamide. Benzolamide administration to hydropenic rats decreased SNGFR by 5.0±1.3 nl/min and AIIA infusion in these rats completely restored SNGFR to the control, prebenzolamide values. These results occurred when SNGFR was measured in both proximal and distal tubules. In another group of hydropenic rats prior AIIA infusion completely prevented any alteration in SNGFR with benzolamide administration (33.0±2.8 vs. 32.3±1.5 nl/min). Benzolamide administration did increase the late proximal tubular flow rate during AIIA infusion (17.2±1.1 to 23.4±1.1 nl/min,P<0.01), demonstrating that AIIA did not act by preventing the diuretic action of benzolamide in the proximal tubule. AIIA infusion alone did not alter control SNGFR or nephron plasma flow, suggesting that the effect of AIIA was not that of a non-specific vasodilator. These studies suggest that the renal vasoconstriction and reduction in SNGFR which results from benzolamide administration is mediated by the local action of angiotensin II.