Comparison of systemic and intrarenal converting enzyme inhibition by MK-422 on renal hemodynamics in conscious dogs.
The purpose of this study was to compare the effect of intrarenal angiotensin converting enzyme (ACE) inhibition with that of systemic ACE inhibition in conscious, instrumented dogs. Intrarenal ACE inhibition was achieved by infusing the potent ACE inhibitor MK-422 into the renal artery in a dose (0.32 micrograms/kg/min) that in dogs fed a normal sodium (n = 11) and low sodium (n = 10) diet markedly attenuated the renal blood flow response to intrarenal arterial angiotensin I (0.4 and 0.8 micrograms, respectively). Intrarenal arterial infusion of MK-422 decreased the responses by 76 and 72% in the normal and low sodium groups, respectively, but only decreased renal vascular resistance slightly (-9 and -8%, respectively) in the infused kidney. Following termination of intrarenal arterial infusion of MK-422, the inhibitor was administered intravenously, 0.2 mg/kg. This dose of MK-422 maximally inhibited systemic ACE, as evidenced by the complete abolition of the renal blood flow response to intravenous angiotensin I; the responses were decreased by 95 and 96% in the normal and low sodium groups, respectively. In contrast to the negligible reduction in renal vascular resistance seen during intrarenal arterial infusion of MK-422, systemically administered inhibitor decreased renal vascular resistance by 16 and 39%, respectively, in the normal and low sodium groups. These results lend additional support to our contention that systemically rather than intrarenally formed angiotensin II is mainly responsible for regulation of renal vascular resistance.
B G
BG
Zimmerman
C J
CJ
Finis
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D015773:Enalaprilat; D005260:Female; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D012077:Renal Artery / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D000804:Angiotensin II; D000803:Angiotensin I; D012964:Sodium; D012083:Renin; D015773:Enalaprilat