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R C Blantz

Publications and source records attributed to R C Blantz.

At least 145 records · Page 8Linked to original sources
PubMed1979

Acute reversal by saralasin of multiple intrarenal effects of angiotensin II.

Glomerular hemodynamics were measured by micropuncture technique in the plasma volume-expanded Munich-Wistar rat in 1) a control group, 2) during a pressor infusion of angiotensin II (AII), and 3) during simultaneous infusions of AII and saralasin, which returned arterial pressure to normal. Respective values obtained in the three groups studied were: nephron filtration rate: 60 +/- 2 vs. 40 +/- 2 vs. 42 +/- 2 nl.min-1.g kidney wt-1; nepphron plasma flow: 263 +/- 13 vs. 106 +/- 5 vs. 165 +/- 13 nl. min-1.g kidney wt-1; LpA, the glomerular permeability coefficient: 0.090 +/- 0.009 vs. 0.033 +/- 0.005 vs. 0.103 +/- 0.020 nl.s-1.g kidney wt-1. mmHg-1; afferent arteriolar resistance: 10.2 +/- 0.7 vs. 25.1 +/- 1.3 vs. 19.7 +/- 3.3 10(9) dyn.s.cm-5; efferent arteriolar resistance: 7.8 +/- 0.5 vs. 22.0 +/- 0.9 vs. 10.8 +/- 1.7 10(9) dyn.s.cm-5. Saralasin acutely reversed the effect of AII on both efferent resistance and LpA, suggesting that AII does not decrease LpA by inducing a fixed anatomic change. For unclear reasons, saralasin did not reverse the increase in afferent resistance associated with infusion of AII. Saralasin infusion in high AII states may acutely affect glomerular hemodynamics by decreasing efferent resistance and increasing the glomerular permeability coefficient.

Angiotensin II↗
PubMed1979

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.

Angiotensin II↗
PubMed1978

Determinants of proximal tubular reabsorption as mechanisms of glomerulotubular balance.

The determinants of absolute proximal reabsorption (APR) were studied in four groups of rats during hydropenia, partial renal vein occlusion (RVO), saline expansion, and RVO after saline expansion. Nephron filtration rate (SNGFR), nephron plasma flow (RPF), APR, and proximal tubule (Pt) peritubular capillary (HPc), and interstitial (HPi) hydrostatic pressures were measured by micropuncture techniques. Subcapsular space (pii) and star peritubular capillary (piE) oncotic pressures were also determined. The peritubular capillary permeability coefficiency (LpAR) and the corresponding effective reabsorptive pressure (ERP) were computed, where APR = LpAR . ERP, and ERP = net reabsorptive pressure across the peritubular capillary. The results indicate that APR correlates best with SNGFR (P less than 0.05), but not with (pii - HPi), RPF, or LpAR. There was a significant relationship between piE and LpAR, where LpAR fell with increases in piE (P less than 0.01). In conclusion, 1) changes in absolute proximal reabsorption correlate best with changes in nephron filtration rate but not with (pii - HPi) across this range of values, 2) changes in efferent oncotic pressure (piiE) correlated inversely with LpAR, and 3) glomerulotubular balance in the proximal tubule can be partially attributed to intraluminal factors.

Animals↗
PubMed1978

The acute effects of antiglomerular basement membrane antibody upon glomerular filtration in the rat. The influence of dose and complement depletion.

Recent studies from this laboratory have revealed that single nephron filtration rate (sngfr) decreases significantly within 1 h of the administration of large doses of complement-fixing antiglomerular basement membrane antibody (AGBM Ab) in plasma-expanded Munich-Wistar rats. This reduction in sngfr was due to decreases in nephron plasma flow (rf) and the glomerular permeability coefficient (LpA) utilizing direct evaluation of all pertinent pressures, flows, and permeabilities. With identical micropuncture techniques, we have determined (a) the respective influences of rpf and LpA upon sngfr by examining the effects of differing doses of AGBM Ab, and (b) the specific effect of complement fixation upon the reduction in sngfr. In normal rats, low dose (1.4 microgram/g body wt) AGBM Ab decreased sngfr from 57.9 +/- 3.4 to 50.8+/- 3.9 nl/min per g kidney wt (kw) (P less than 0.001), and this was due to a 10% reduction in rpf and a decrease in LpA FROM 0.069 +/- 0.014 in control to 0.041 +/- 0.007 nl/s per g kw per mm Hg (P less than 0.02). At the high dose (2.3 microgram/g body wt), sngfr fell dramatically from 58.4 +/- 4.0 to 7.6 +/- 3.8 nl/min per g kw (P less than 0.001), and this effect upon filtration was the result of an 86% reduction in rpf and a decrease in LpA from 0.092 +/- 0.020 to 0.007 +/- 0.004 nl/s per g kw mm Hg (P less than 0.001). Therefore, at lower doses sngfr fell primarily as a result of a 40% reduction in LpA and a 10% decrease in rpf; however, at the high dose massive reductions in both rps and LpA led to the large decrease in sngfr. In complement-depleted rats, receiving identical doses, low-dose AGBM Ab no longer reduced the sngfr, but a reduction in LpA persisted (other factors compensating to maintain sngfr). At the high dose, complement depletion ameliorated the reduction in sngfr (55.1 +/- 2.4 to 37.2 +/- 3.4 nl/min per g kw mm Hg) by nearly eliminating the vasoconstriction but only partially diminished the reduction in LpA (0.097 +/- 0.020 to 0.032 +/- 0.004 nl/s per g kw mm Hg, P less than 0.05). Complement depletion prevented the migration of polymorphonuclear leukocytes (present in larger numbers after the high dose of AGBM Ab) into the capillary and eliminated vasoconstriction. Complement depletion resulted in a lesser effect of high-dose AGBM Ab upon LpA than in normal rats, and this is likely due to lesser polymorphonuclear leukocyte effects upon capillary surface area. The persistent reduction in LpA observed in complement-depleted rats correlated with separation of the endothelial cell from the glomerular basement membrane after AGBM Ab, AGBM Ab diminished glomerular ultrafiltration by decreasing LpA and altering the endothelial surface of the glomerular membrane, and this effect is not totally dependent upon the fixation of complement.

Animals↗
PubMed1978

Studies on the tubulo-glomerular feedback system in the rat. The mechanism of reduction in filtration rate with benzolamide.

The specific mechanism whereby superficial nephron glomerular filtration rate (sngfr) is reduced after the administration of benzolamide, a carbonic anhydrase inhibitor with a primary inhibitory effect in the proximal tubule, have been examined by measuring pertinent pressures, flows, and glomerular permeabilities in the hydropenic Munich-Wistar rat, a strain with surface glomeruli. Because benzolamide decreases absolute proximal reabsorptive rate, the rate of delivery of tubular fluid to the distal nephron should be at least transiently increased and may reduce sngfr by activating the tubulo-glomerular feedback system. Sngfr fell from 29.2+/2.0 to 2.1+/3.1 nl/min (P less than 0.01) after benzolamide (group 1), a percentage reduction equal to kidney glomerular filtration rate and similar to sngfr obtained in collections from distal tubules. Separate studies (group 2) revealed that if transient increases in distal nephron delivery were prevented by insertion of a long oil block in proximal tubules before control, the decrease in sngfr was prevented (30.3+/1.0 vs. 30.3+/1.8 nl/min, P greater than 0.9). In paired "unblocked" nephrons in the same rats, sngfr fell in group 2 (33.0+/1.0 vs. 25.2+/2.3 nl/min, P less than 0.01). In "blocked" nephrons in which sngfr reduction was prevented, the rate of fluid leaving the proximal tubule increased from 16.9+/ to 23.1+/1.0 nl/min (P less than 0.01). In group 1 studies in which sngfr fell and transient increases in flow out of the last segment of the proximal tubule (distal delivery) (approximately equal to 8 nl/min) were not prevented, steady-state distal delivery was unchanged by benzolamide (13.9+/1.1 vs. 14.2+/2.2 nl/min). Also, sngfr returned toward control, pre-benzolamide values, when a proximal oil block was placed for 15 min and the rate of distal delivery reduced after benzolamide administration, which suggests that this activation was reversible. These data suggest that activation of tubulo-glomerular feedback by transient increases in distal delivery was responsible for decreases in sngfr. Analysis of all determinants of glomerular ultra-filtration revealed that the efferent mechanism leading to reduced sngfr after benzolamide was decreased nephron plasma flow (101+/13 vs. 66+/13 nl/min, P less than 0.01). Hydrostatic pressure and the glomerular permeability coefficient did not contribute to reductions in sngfr with benzolamide. Because the rate of distal delivery remained constant in spite of large changes in both sngfr and absolute proximal reabsorptive rate, it is suggested that the rate of distal delivery may be the physiologic entity that is regulated by the tubulo-glomerular feedback system via alterations in sngfr.

Animals↗
PubMed1977

Factors determining superficial nephron filtration in the mature, growing rat.

Factors that determine and cause an increased glomerular filtration rate in superficial nephrons (sngfr) in the mature, growing rat were examined in 39 Munich-Wistar rats, ranging from 93 to 335 g in body weight, from 40 to 140 days in age, and in sngfr, from 15 to 78 nl/min. Hydrostatic pressure gradient (delta P) from glomerular capillary (PG) to Bowman's space (Pt) was measured in surface glomeruli and pertinent oncotic pressures (pi) by microprotein methods. Isoncotic plasma expansion (PV) prevented filtration-pressure equilibrium (EFP) and permitted calculation of glomerular permeability coefficient (LpA) where sngfr = EFP-LpA, and EFP = delta P - pi. Increased sngfr correlated best with nephron plasma flow (rpf) (r = 0.81, P less than 0.001) and LpA (r = 0.71, P less than 0.001). The rpf increased because of parallel reductions in afferent and efferent resistances (slope = 0.89 +/- 0.09, r = 0.86, P less than 0.001), which also produced a constancy of PG and deltaP with growth. The ratio of rpf to LpA remained constant with growth permitting EFP to remain relatively unchanged (r = 0.14, P greater than 0.4). The increase in LpA should permit filtration-pressure equilibrium to persist in the hydropenic rat in spite of increases in rpf with growth. deltaP was constant with increasing age and therefore did not contribute to the increase in sngfr.

Aging↗
PubMed1977

An analysis of the determinants of nephron filtration rate.

Studies on glomerular filtration in the Munich-Wistar rat, a strain with surface glomeruli, have permitted for the first time the evaluation of the four factors that determine filtration rate: 1) the rate of nephron plasma flow (RPF), 2) the glomerular hydrostatic pressure gradient (deltaP) from capillary to Bowman's space, 3) systemic oncotic pressure (piA), and 4) the glomerular permeability coefficient (LpA), and their respective roles in producing change in filtration rate. The process of filtration in the Munich-Wistar rat is characterized by filtration pressure equilibrium and, therefore, filtration should be highly plasma flow-dependent. Analysis of data from this strain suggests that multiple factors can change LpA, and, at least in animals which do not achieve filtration pressure equilibrium, these alterations in LpA can influence the final filtration rate. Multivariate statistical analysis in a variety of experimental conditions in the Munich-Wistar rat suggest that changes in RPF remain the major mediator of change in nephron filtration rate, both in rats at filtration pressure equilibrium and in disequilibrated animals. Although the glomerulus is an ultrafilter driven by hydrostatic forces, changes in deltaP assume a lesser role in producing alterations in filtration rate.

Angiotensin II↗
PubMed1977

Renal lymph protein in the rat.

Renal lymph and systemic (posterior) lymph were studied in hydropenic rats. As a consequence of the anatomical arrangement of collecting lymphatics near the kidney, mixed renal and systemic lymph tributaries are situated in such a way that sampling pure renal lymph is difficult. Pure renal lymph contains 1.0 +/- 0.1 g/100 ml total protein with an albumin-to-globulin (A/G) ratio of 2.1 +/- 0.1. Mixed renal and extrarenal lymphatic tributaries contain 3.3 +/- 0.2 g/100 ml total protein with an A/G ratio of 1.8 +/- 0.2. Corresponding values in the plasma are 4.9 +/- 0.2 and 1.2 +/- 0.1 g/100 ml, respectively. Previous studies in which the concentration of renal lymph protein was determined as 30-50% of that in plasma were probably in error due to contamination of renal samples by posterior lymph ducts. The amount of systemic and renal lymph mixing is highly variable from one animal to another. Our renal lymph samples in carefully controlled and prepared Munich-Wistar rats contained a total protein uniformly 20% of that in plasma.

Albumins↗
PubMed1977

Relation of distal tubular delivery and reabsorptive rate to nephron filtration.

The tubuloglomerular feedback hypothesis states that filtration rate in a single nephron unit (SNGFR) is controlled or modified through variations in the rate of either distal delivery or tubular reabsorption in that same nephron. We have reexamined this hypothesis by varying the perfusion rate of the late proximal tubule from normal (10 nl/min) to supranormal values (30 nl/min) in a reversible fashion and measured the resultant nephron filtration rate. Three perfusion fluid were utilized: group I, a solution simulating late proximal tubular fluid (11 mM HCO3); group II, a solution with a higher HCO3 concentration (30 mM HCO3); and group III, a solution simulating early proximal tubular fluid. In group I SNGFR was 27.2 nl/min during perfusion from the late proximal tubule at 10 nl/min and fell to 19.8 nl/min during the 30 nl/min perfusion rate. Group II SNGFR was 27.7 nl/min at the 10 nl/min rate and 19.0 nl/min during the 30 nl/min perfusion. Groups I and II then demonstrated a completely reversible tubuloglomerular feedback response. In group III, the SNGFR at 10 nl/min was 26.2 nl/min and 23.4 nl/min at the 30 nl/min perfusion rate and were significantly different. Evaluation of collections of distal tubule fluid in perfused nephrons revealed that increased absolute reabsorption of water and chloride between late proximal and distal tubules was associated with the reductions in SNGFR in the same nephron. A strong candidate for the afferent limb of this system is the change in absolute chloride reabsorption between late proximal and distal tubules.

Animals↗
PubMed1976

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 Bowman's 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.

Angiotensin II↗
PubMed1976

Acute effects of antiglomerular basement membrane antibody on the process of glomerular filtration in the rat.

Nehron filtration rate (sngfr) and the factors controlling filtration were examined before and with 60 min of the intravenous infusion of 225-450 mug of antiglomerular basement membrane antibody (AGBM Ab) (greater than 50% antigenic saturation) in plasma-expanded (2.5% body wt) Munich-Wistar rats. Pressures in glomerular capillaries (PG) and bowman's space (Pt) were measured with a servo-nulling device, systemic (piA) and efferent arteriolar oncotic pressures (piE) were measured by microprotein methods, and nephron plasma flow (rpf) and sngfr were measured by micropuncture techniques in both control and post-AGBM Ab conditions in each rat. The sngfr fell from 52.7+/-2.9 to 24.1+/-1.9 nl/min per g kidney wt (n = 7, P less than 0.001). Both afferent and efferent arteriolar resistances increased and rpf fell from 221+/-25 to 90+/-9 nl/min per g kidney wt (P less than 0.001) but the hydrostatic pressure gradient across the glomerular membrane deltaP = PG - Pt) increased from 37+/- 1 to 50+/-2 mm Hg (P less than 0.001). The increase in deltaP and a numerical decrease in piA both acted to maintain sngfr after AGBM Ab and effectively nullified the influence of decreased rpf upon sngfr. The mean effective filtration pressure (EFP = deltaP - pi) increased from 14+/-2 to 30+/-3 mm Hg (P less than 0.001) while sngfr decreased. The major and critical reason for this reduction in sngfr was a decrease in the glomerular permeability coefficient from 0.077+/-0.017 to 0.014+/-0.001 nl/s per g kidney wt per mm Hg P less than 0.001) where sngfr=EFP-LpA.

Animals↗
PubMed1975

Determinants of peritubular capillary fluid uptake in hydropenia and saline and plasma expansion.

Hydrostatic (HPc) and oncotic (phic) pressures within the peritubular capillary, tubular pressure (Pt), nephron filtration rate, and plasma flow, and proximal fractional and absolute reabsorption (APR) were measured in anesthetized rats during hydropenia and plasma and saline expansion. Net interstitial pressure (phii-HPi) was estimated from subcapsular hydrostatic and oncotic pressures during saline expansion and these data were applied to a mathematical model of peritubular capillary fluid uptake to determine the profile of effective reabsorption pressure (ERP) with distance (x*) alongthe capillary and calculate the peritubular capillary permeability coefficient (LpAr). ERPX* = (PHIC MINUS HPC)X* MINUS (PHII MINUS HPi) and APR = ERPX*LpAr. During saline expansion phii minus HPi was -12.1 plus or minus 0.8 mmHg and ERP,3.8 mm. The LpAr was 0.07 nl/s per g KW per mmHg, and this value was applied to hypropenia and plasma expansion to determine ERP and phii minus HPi. The phiiminus HPi was +6.0 and +5.0 mmHg, respectively, and ERP was 4.1 and 3.5 mmHg. Efective reabsorptive pressure remained positive along x* in all states, and phii minus HPi correlated best changes in phic and poorly with changes in efferent plasma flow. The APR did not correlate with either calculated phii minus HPi or the transepithelial driving pressure, Pt + phii minus HPi.

Absorption↗
PubMed1975

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 Bowman's space pressure (Pt) were measured directly in surface glomeruli with a servonulling device (deltaP = PG - PT), systemic (piA) and efferent (piE) 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 = deltaP - pi) 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 nilters/min g-1 kidney weight (P less than 0.025) with elevated ureteral pressure entirely as a result of a decrease in the hydrostatic pressure gradient (deltaP), 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 less than 0.001) due to an increase in vascular resistance between the peritubular capillaries and the renal vein which prevented the reduction in deltaP. The reduction in sngfr appeared to result from a reduction in LpA 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.

Animals↗
PubMed1975

The mechanism of acute renal failure after uranyl nitrate.

Administration of 25 mg/kg uranyl nitrate (UN) to rats leads to a brief period of polyuria followed by progressive oliguria with death at 5 days. Factors that determine glomerular filtration rate (GFR) were examined in control Munich-Wistar rats (n equals 16) and 2 h after either 15 mg/kg (n equals 8) or 25 mg/kg (n equals 7) of UN (i.v.) utilizing direct measurements of hydrostatic and oncotic pressures and plasma flow. Total kidney GFR was reduced to 47% of control in the low dose group and to 21% in the high dose group. The simultaneous nephron filtration rate (sngfr) was 28.6 plus or minus 0.8 nl/min/g kidney wt in control, 29.1 plus or minus 1.0 in the low dose group, and 18.1 plus or minus 1.2 (P less than 0.001) in the higher dose group. This disparity in UN effect upon GFR and sngfr was due to tubular back-diffusion of solute through damaged epithelia beyond the early proximal tubule as demonstrated by microinjection of inulin and mannitol in the proximal tubule. Inulin "leak" persisted at 6 h after UN when tubular pressure had returned to normal. Comparison of sngfr measured in early vs. late proximal tubule revealed no difference after high dose UN, suggesting no significant leak of inulin from the early proximal tubule, and that the decreased sngfr was due to primary reductions in ultrafiltration. Nephron plasma flow was equal to control at both doses of UN. Also directly measured hydrostatic pressure gradient across the glomerular capillary was not changed. The effective filtration pressure achieved equilibrium in control of animals but became significantly positive at the efferent end of the capillary at both doses of UN and increased. Total glomerular permeability (LpA) was progressively reduced from control (0.089 plus or minus 0.005 nl/s/g kidney wt/mm Hg) at low dose UN (0.047 plus or minus 0.013) and high dose 0.024 plus or minus 0.003 nl/s/g kidney wt/mm Hg). Therefore UN decreases GFR by two mechanisms: (1) tubular damage leading to back-diffusion of solutes and (b) a primary reduction in sngfr due to reduced LpA.

Acute Kidney Injury↗
PubMed1974

Effect of mannitol on glomerular ultrafiltration in the hydropenic rat.

The effect of mannitol upon glomerular ultrafiltration was examined in hydropenic Munich-Wistar rats. Superficial nephron filtration rate (sngfr) rose from 32.0+/-0.9 nl/min/g kidney wt to 42.0+/-1.6 (P < 0.001) in eight rats. Hydrostatic pressure gradients acting across the glomerular capillary (DeltaP) were measured in glomerular capillaries and Bowman's space with a servo-nulling device, systemic (piA) and efferent arteriolar oncotic pressures (piE) were determined by microprotein analysis. These data were applied to a computer-based mathematical model of glomerular ultrafiltration to determine the profile of effective filtration pressure (EFP = DeltaP - pi) and total glomerular permeability (L(p)A) in both states. Filtration equilibrium obtained in hydropenia (L(p)A >/= 0.099+/-0.006 nl/s/g kidney wt/mm Hg) and sngfr rose because EFP increased from a maximum value of 4.2+/-1.1 to 12.8+/-0.5 mm Hg after mannitol (P <0.01). This increase was due to both increased nephron plasma flow and decreased piA. Computer analysis of these data revealed that more than half (>58%) of this increase was due to decreased piA, consequent to dilution of protein. Since EFP was disequilibrated after mannitol, L(p)A could be calculated accurately (0.065 +/- 0.003 nl/s/g kidney wt/mm Hg) and was significantly lower than the minimum estimate in hydropenia.Therefore, sngfr does increase with mannitol and this increase is not wholly dependent upon an increase in nephron plasma flow since the major factor increasing EFP was decreased piA.

Animals↗