Control of renal function by intrarenal angiotensin II in the dog.
The purpose of this study was to determine if conversion of angiotensin I to angiotensin II (Ang II) within the kidney is important in the control of renal function following sodium depletion. Infusion of a short-acting angiotensin I-converting enzyme (ACE) inhibitor, BPP5a, into the left kidney at a dose of 30 micrograms/kg/min failed to alter significantly the pressor response to Ang I administered in a femoral vein. Mean arterial pressure and renal function in the contralateral noninfused kidney also remained unchanged to intrarenal infusion of the ACE inhibitor into the left kidney. Thus, the ACE inhibitor used in these studies can be effectively localized to the renal circulation when infused intrarenally at 30 micrograms/kg/min. Intrarenal infusion of the ACE inhibitor at 30 micrograms/kg/min into sodium-restricted dogs failed to alter renal blood flow (RBF) significantly. However, the glomerular filtration rate (GFR), urine volume, and sodium excretion all increased significantly in response to intrarenal ACE inhibition. Intrarenal Ang II generation therefore appears to play a physiologically important role in the control of GFR, urine volume, and sodium excretion but not RBF following sodium depletion. The increase in GFR following intrarenal infusion of the ACE inhibitor may suggest that Ang II is formed mainly at glomerular or preglomerular sites.
Levens
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Research Department, Ciba-Geigy Corporation, Summit, New Jersey.
D000704:Analysis of Variance; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A