Effect of exogenous and endogenous angiotensin II on intrarenal distribution of glomerular filtration rate in rats.

Abstract

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 pentobarbitone-anaesthetised 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.(125)I-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)I-labelled 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)), where subscripts E and C stand for experimental and control, respectively. F values greater than 1.00 directly indicate and quantify a relatively greater increase of filtration rate in inner than in outer cortex. We found in salt-replete rats that at practically unchanged total GFR, intravenous and intra-arterial infusion of AngII increased F to 1.07 and 1.04 (P < 0.05) whereas losartan reduced F to 0.99. After pretreatment with the inhibitor of nitric oxide production L-NAME, losartan increased total GFR by 8 % and F fell to 0.95 (P < 0.05). In salt-depleted rats losartan reduced F to 0.95 (P < 0.05) at unchanged total GFR. All IC/OC changes induced by losartan were significantly different from that obtained by AngII infusions. We conclude that deep nephrons have higher postglomerular AngII tone and also higher AngII sensitivity than superficial nephrons. The better preserved GFR in deep cortex during AngII action may contribute towards maintaining the renal concentrating ability by providing NaCl for reabsorption by the ascending limb of the loop of Henle.