The effect of the NO synthase blocker N(G)-nitro-L-arginine methyl ester (L-NAME) on glomerular filtration rate (GFR) in outer (OC), middle (MC), and inner cortex (IC) was studied in anesthetized male Sprague-Dawley rats by the aprotinin method. The filtered amount of 125I- and 131I-labeled aprotinin injected before and after L-NAME injection was measured in the same cortical tissue samples after excising the kidney. Arterial pressure increased on average by 43 mmHg, whereas renal blood flow fell by 26% after L-NAME, giving an increase in renal resistance of 92%. At constant renal arterial pressure, resistance rose by only 39%, revealing that autoregulation was responsible for about one-half of the resistance increase. Total and zonal GFR showed a small, statistically insignificant increase after L-NAME, regardless of whether the renal pressure was allowed to rise or not. The response varied considerably among animals, but in each animal the GFR varied proportionately in OC, MC, and IC. We conclude that the vasodilator tone of NO is predominantly located in postglomerular resistance vessels and is similar in the three cortical layers.

Exogenous angiotensin II (AngII) has a marked vasoconstrictor effect on most vascular beds, including the kidney. More important, a constant intrarenal formation of AngII, regulated mainly through renin release by the juxtaglomerular apparatus, provides a sustained contribution to vascular tone and resistance. A large number of studies have shown that AngII infusion causes relatively greater reduction of renal blood flow (RBF) than of glomerular filtration rate (GFR) and an increase in the filtration fraction, suggesting a preferential vasoconstriction in postglomerular resistance vessels (Navar et al. 1996). More conflicting results have been obtained on a possible preferential reduction of RBF in deep or superficial cortical layers, possibly due to a variable counter-regulation by prostaglandins or nitric oxide (NO) formation (Aiken & Vane, 1973;Aukland, 1976;Mattson & Roman, 1991;Hura & Stein, 1992;Pallone, 1994;Navar et al. 1996).In the 1970s many GFR distribution studies were performed using the Hanssen ferrocyanide technique (Hanssen, 1963) to test the hypothesis that renal sodium chloride excretion could be determined by the relative filtration rate in deep and superficial cortex. As summarized by Lameire et al. (1977) the results obtained in rats on varying salt intake Different changes in glomerular filtration rates (GFR) in deep and superficial glomeruli have been suggested to influence renal NaCl excretion and concentrating ability. Angiotensin II (AngII) has been implicated in such changes, but the experimental evidence has been conflicting, probably because of the methodological limitation of just one 'snapshot' measurement of local GFR per kidney. We have therefore studied the effect of AngII and AT 1 -receptor blockade on glomerular filtration in outer, middle and inner cortex (OC, MC and IC, respectively) in pentobarbitoneanaesthetised rats using the aprotinin (Ap) method, providing control and experimental measurements in the same kidney. Glomerular filtration rate per gram cortical tissue was measured based on 'free' glomerular filtration of Ap followed by complete tubular uptake and a 20 min sojourn in the proximal tubular cells before breakdown and incipient return to the plasma. Effect of exogenous and endogenous angiotensin II on intrarenal distribution of glomerular filtration rate in rats 125I-labelled Ap was injected I.V. to determine control Ap clearance, followed after 13 min by injection of AngII or the A1 type AngII receptor blocker losartan and 2 min thereafter by 131 Ilabelled Ap to determine clearance in the experimental period. Tracer activity in frequent blood samples and in tissue samples allowed calculation of GFR in the two periods. Mean GFR control values were: 1.13 ml min _1 in whole kidney and 1.44, 1.27 and 0.76 ml min _1 per gram cortical tissue in OC, MC and IC, respectively. The most sensitive and comprehensive measure of altered GFR distribution is the ratio between the relative filtration change in inner versus that in outer cortex, F = (IC E /IC C )/(OC E /OC C ), w...