Reversible hemodynamic defect in glomerular filtration rate after ischemic injury.

In Wistar rats with surface glomeruli 3 h of nearly complete occlusion of the left renal artery resulted in uniform falls (similar to50%) in ipsilateral whole-kidney glomerular filtration rate (GFR) and single-nephron GFR (SNGFR) and in urinary findings consistent with impaired water reabsorption. Since the fall in SNGFR was accompanied by a proportional fall in glomerular plasma flow rate (GPF), and since net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary was unchanged from preischemic levels, these findings suggest that the fall in SNGFR was a hemodynamic consequence of the fall in GPF. To test this hypothesis, GPF was restored to preischemic levels by means of acute infusion of homologous, isoncotic plasma. GPF and SNGFR uniformly increased, on average to preischemic levels, whereas net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary again remained essentially unchanged. These studies demonstrate that the fall in SNGFR in this model of ischemic injury is causally related to the accompanying fall in GPF. Of interest, despite this reversal of the defect in GFR, fractional water reabsorption remained impaired. This restoration of GFR but not reabsorption by plasma infusion abruptly converts this ischemic lesion from nondiuretic to diuretic.

Determinants of glomerular filtration in experimental glomerulonephritis in the rat.

Pressures and flows were measured in surface glomerular capillaries, efferent arterioles, and proximal tubules of 22 Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). Linear deposits of rabbit and rat IgG and C3 component of complement were demonstrated in glomerular capillary walls by immunofluorescence microscopy. Light microscopy revealed diffuse proliferative glomerulonephritis, and proteinuria was present. Although whole kidney and single nephron glomerular filtration rate (GFR) in NSN (0.8 plus or minus 0.04 SE2 ml/min and 2 plus or minus 2 nl/min, respectively) remained unchanged from values in 16 weight-matched NORMAL HYDROPENIC control rats (0.8 plus or minus 0.08 and 28 plus or minus 2), important alterations in glomerular dynamics were noted. Mean transcapillary hydraulic pressure difference (deltaP) averaged 41 plus or minus 1 mm Hg in NSN versus 32 plus or minus 1 in controls (P LESS THAN 0.005). Oncotic pressures at the afferent (piA) end of the glomerular capillary were similar in both groups ( 16 mm /g) but increased much less by the efferent end (piE) in NSN (to 29 plus or minus 1 mm Hg) than in controls (33 plus or minus 1, P less than 0.025). Hence, equality between deltaP and piE, denoting filtration pressure equilibrium, obtained in control but not in NSN rats. While glomerular plasma flow rate was slightly higher in NSN (88 plus or minus 8 nl/min) than in controls (76 plus or minus 6, P greater than 0.2), the failure to achieve filtration equilibrium in NSN rats was primarily the consequence of a marked fall in the glomerular capillary ultrafiltration coefficient, Kf, to a mean value of 0.03 nl/(s times mm Hg), considerably lower than that found recently for the normal rat, 0.08 nl/(s times mm Hg). Thus, despite extensive glomerular injury, evidenced morphologically and by the low Kf, GFR remained normal. This maintenance of GFR resulted primarily from increases in deltaP, which tended to increase the net driving force for filtration, and thereby compensate for the reduction in Kf.

Dynamics of glomerular ultrafiltration in the rat. V. Response to ischemic injury.

An experimental model of postischemic, acute renal failure has been developed in Wistar rats with surface glomeruli, thereby making possible a direct assessment of the mechanisms responsible for the fall in glomerular filtration rate that characterizes this disorder. Whole kidney and cortical single nephron filtration rates were reduced proportionately, on average by approximately 40%, after 3 h of nearly complete occlusion of the ipsilateral renal artery. The possibility of a significant transtubular leak of inulin was excluded. This decline in filtration rate occurred in the absence of measured changes in mean arterial pressure, mean glomerular transcapillary hydrostatic pressure, or net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary. Net ultrafiltration pressure at the efferent end of the capillary approached zero both before and after ischemic injury, demonstrating that filtration pressure equilibrium was achieved throughout this study. Single nephron filtration fraction remained unchanged, indicating that the fall in filtration rate was accompanied by a proportional decline in glomerular plasma flow. The results indicate that the fall in filtration rate was solely the consequence of this fall in glomerular plasma flow. Since filtration rate per nephron is equal to the product of the ultrafiltration coefficient and mean ultrafiltration pressure, this product must also have fallen in proportion to the decline in glomerular plasma flow. Evidence is presented to indicate that a change in ultrafiltration coefficient is not required to account for the observed fall in filtration rate. The reduction in glomerular plasma flow, occuring in the absence of a concomitant decline in mean glomerular capillary hydrostatic pressure, resulted from large and proportional increases in afferent and efferent arteriolar resistances. These resistance changes appear to play a fundamental role in the pathogenesis of this form of acute renal failure.

Quantitative importance of changes in postglomerular colloid osmotic pressure in mediating glomerulotubular balance in the rat.

In recent studies in this laboratory employing normal hydropenic rats we have demonstrated that the reduction in absolute proximal reabsorption that attends the experimental reduction of single nephron glomerular filtration rate (SNGFR) (glomerulotubular balance) is mediated, at least in part, by the accompanying decline in postglomerular vascular protein concentration, and therefore, postglomerular colloid osmotic pressure (piEA). The present study was undertaken to define the quantitative contribution of these changes in piEA to the changes in absolute proximal reabsorption measured under these conditions. A protocol was employed which enabled us to examine the effects on absolute proximal reabsorption of reductions in filtered load brought about under conditions in which piEA remained essentially unchanged. Thus, after partial aortic constriction in 16 plasma-loaded rats, near constancy of piEA was observed in 10 (a change in efferent arteriolar protein concentration of 0.4 g/100 ml or less) and in these, uniform reductions in SNGFR averaging 16.7 nl/min were attended by reductions in absolute proximal reabsorption averaging only 1.7 nl/min, or 7% of preconstriction values. These findings, taken together with previous observations from this laboratory, suggest that the proximal reabsorptive adjustment that characterizes glomerulotubular balance in the rat is markedly blunted when changes in piEA are prevented. In the remaining six rats, a mean reduction in filtered load comparable to that observed in the above group was attended by slightly to moderately greater reductions in efferent arteriolar protein concentration, thereby fulfilling less well the stated aim of this study. Nevertheless, in accord with the above conclusion, these relatively greater reductions in piEA were accompanied by correspondingly greater reductions in absolute proximal reabsorption.

Renal response to chronic intravenous salt loading in the rat.

The natriuresis of acute Ringer's loading is associated with a rise in the rate of delivery of fluid beyond the proximal tubule due both to a rise in glomerular filtration and a fall in absolute reabsorption, the latter being causally mediated, at least in part, by the accompanying fall in postglomerular vascular [protein]. To determine whether these factors also contribute to the renal response to chronic Ringer's loading, nine rats given continuous infusions, 30% body weight/day over 5-14 days, were studied using free-flow micro-puncture techniques. Results were compared with data from 10 chronic control rats given less than 1.5% body wt/day. Late proximal tubule fluid-to-plasma [inulin] ratios, (TF/P)(IN), single nephron glomerular filtration rate (SNGFR), absolute proximal reabsorption, and postglomerular vascular [protein] in chronic control rats and chronically loaded rats averaged 2.2+/-SE 0.1 (n = 35) and 1.5+/-0 (35), P<0.001; 37+/-2 (35) and 47+/-4 nl/min (35), P<0.05; 19+/-1 (35) and 16+/-2 nl/min (35), P>0.2; and 9.5+/-0.3 (8) and 8.6+/-0.3 g/100 ml (8), P>0.05, respectively. Thus the fall in (TF/P)(IN) and the rise in distal delivery during chronic Ringer's loading were due almost entirely to the rise in SNGFR, and not to any large fall in absolute reabsorption. Hence chronic and acute Ringer's loading increase delivery of proximal tubule fluid by different mechanisms, with chronic sodium homeostasis being governed overwhelmingly by adjustments in GFR. When, however, an acute Ringer's load was infused into chronically loaded rats, we observed significant and parallel reductions in absolute proximal reabsorption and postglomerular vascular [protein]. These findings suggest that the difference between the effects of chronic vs. acute Ringer's loading on absolute proximal reabsorption may have been due, at least in part, to the corresponding difference in the effects these two loading procedures have on postglomerular vascular [protein].

The dynamics of glomerular ultrafiltration in the rat.

Using a unique strain of Wistar rats endowed with glomeruli situated directly on the renal cortical surface, we measured glomerular capillary pressures using servo-nulling micropipette transducer techniques. Pressures in 12 glomerular capillaries from 7 rats averaged 60 cm H(2)O, or approximately 50% of mean systemic arterial values. Wave form characteristics for these glomerular capillaries were found to be remarkably similar to those of the central aorta. From similarly direct estimates of hydrostatic pressures in proximal tubules, and colloid osmotic pressures in systemic and efferent arteriolar plasmas, the net driving force for ultrafiltration was calculated. The average value of 14 cm H(2)O is lower by some two-thirds than the majority of estimates reported previously based on indirect techniques. Single nephron GFR (glomerular filtration rate) was also measured in these rats, thereby permitting calculation of the glomerular capillary ultrafiltration coefficient. The average value of 0.044 nl sec(-1) cm H(2)O(-1) glomerulus(-1) is at least fourfold greater than previous estimates derived from indirect observations.

On the mechanism of inhibition in fluid reabsorption by the renal proximal tubule of the volume-expanded rat.

We undertook to determine the extent to which the inhibition in absolute proximal fluid reabsorption in response to expansion of extracellular volume with noncolloid-containing solutions is the result of concomitant reductions in postglomerular (efferent arteriolar) protein concentration. Selective elevation of efferent arteriolar oncotic pressure in volume-expanded rats (Ringer's 10% body weight) to levels slightly in excess of normal by microperfusion with 9-10% albumin-Ringer's solution nearly completely reversed the inhibition in absolute and fractional reabsorption in adjacent proximal tubules. In contrast, during similar microperfusion with a 6-7% albumin solution, no increase in proximal reabsorption was measured. We interpret these findings to indicate that the bulk of the inhibition in absolute proximal reabsorption in response to volume expansion with colloid-free solutions is causally mediated by the accompanying parallel decline in postglomerular vascular protein concentration.