Bilateral renal function responses to converting enzyme inhibitor (SQ 20,881) in two-kidney, one clip Goldblatt hypertensive rats.

Abstract

SUMMARYThe influence of the renln-angiotensin system on individual kidney function of two-kidney, one clip Goldblatt hypertensive (GH) rats was evaluated by determining renal functional responses during intravenous infusion of converting enzyme inhibitor (CEI) (SQ 20,881, 0 J rag/100 g-hr) for 3.5 bourn. Rats were made hypertensive by placing a 0.25 mm silver clip on the right renal artery 3-4 weeks prior to study. Normal rats and GH rats were prepared to allow urine collections from each kidney. Mean arterial pressure of GH rats fell significantly from preinfusion levels of 153 ± 7 to 126 ± 4 mm Hg during CEI infusion. Despite this decrease in arterial pressure, the nondipped kidneys with reduced renal renin activity (14 ± 5 vs 293 ± 40 ng Al/mg-hr in the clipped kidney) exhibited dramatic increases in gtomerular filtration rate (GFR) (from 1.45 ± 0.06 to 2.56 ± 0.35 ml/mln), urine flow (4.82 ± 0.71 to 9.11 ± 1.19 ^il/mln), sodium excretion (0.10 ± 0.02 to 1.15 ± 0.39 M Eq/mln), fractional sodium excretion (0.05% ± 0.02% to 0.43% ± 0.18%), and potassium excretion (0.94 ± 0.08 to 2.50 ± 0.55 /<Eq/mln). Significant arterial-pressure-associated decreases In GFR, urine flow, and salt excretion were observed in the clipped kidney. In normal rats, CEI infusion produced reductions in arterial pressure and increases in GFR, urine flow, and sodium excretion that were of smaller magnitude than those observed in the nondipped kidneys of GH rats. Plasma renin activity was significantly higher in GH rats than in normal rats (24.0 ± 2.7 vs 12.8 ± 3.4 ng AI/mMir). The augmented renal responses to CEI by the nondipped kidney suggest that elevated circulating angiotensin levels exert a substantial influence on hemodynamic and excretory function of these kidneys even though intrarenal renin activity is markedly reduced. This influence may lead to fluid and electrolyte retention and may partially explain the apparent failure of the nondipped kidney to prevent the development of hypertension.

Renovascular hypertension impairs formation of endothelium‐derived relaxing factors and sensitivity to endothelin‐1 in resistance arteries

“…Increased Miyauchi et al, 1989;Criscione et al, 1990), decreased (Dohi & Luscher, 1990b;Auch-Schwelk & Vanhoutte, 1989) and normal responses (Diederich et al, 1989;Criscione et al, 1990) to endothelin-1 have been reported in vessels from spontaneously hypertensive rats. The responsiveness of resistance arteries to endothelin-1 in renovascular hypertension would be of pathophysiological interest, since this type of hypertension is characterized by an increased activity of the renin-angiotensin system (Brunner et al, 1962;Fourcade et al, 1971;Ploth et al, 1977;Huang et al, 1981;Miyazaki et al, 1986;Wilson et al, 1989) and because angiotensin II stimulates the production of endothelin in cultured endothelial cells (Emori et al, 1989).…”

Intrarenal Angiotensin II Augmentation in Angiotensin II Dependent Hypertension.

“…This responsiveness of the non-clipped kidney to blockade of the reninangiotensin system persists even during the maintenance phase of hypertension when the plasma renin and ANG II concentrations have returned to near normal levels (36,38). The continued influence of ANG II on the non-clipped kidney after circulating levels return towards normal is of critical importance to the hypertensinogenic process (31,33,37,47,49,50).…”

“…In the 2K1C model of renovascular hypertension, hypertension is induced by unilateral stenosis of the renal artery, usually by application of a silver clip. In general, the stenosis is not so severe to cause ischemia and the normal autoregulatory mechanism helps maintain renal blood flow and GFR near normal levels (33). However, the reduced renal perfusion pressure stimulates renin release from the stenotic kidney.…”

“…Renin depletion and reduced renin mRNA levels in the non-clipped kidney have previously been considered as evidence that the activity of the intrarenal renin-angiotensin is greatly diminished in the non-clipped kidney (43,44). However, functional data have demonstrated that the non-clipped kidney is still highly responsive to pharmacological blockade of the renin-angiotensin system with ACE inhibitors or ANG II receptor antagonists (29,31,33,45,46). The non-clipped kidney responds to acute ANG II receptor blockade by increasing sodium excretion, RBF and GFR (33,47).…”

“…However, functional data have demonstrated that the non-clipped kidney is still highly responsive to pharmacological blockade of the renin-angiotensin system with ACE inhibitors or ANG II receptor antagonists (29,31,33,45,46). The non-clipped kidney responds to acute ANG II receptor blockade by increasing sodium excretion, RBF and GFR (33,47).…”