Hemodynamic effects of a new angiotensin converting enzyme inhibitor, spirapril, in sodium-loaded and sodium-depleted rabbits.
The new angiotensin converting enzyme inhibitor, spirapril, was found to inhibit the pressor effects of angiotensin I about 10 times more potently than captopril in conscious rabbits. Its effects on systemic hemodynamics and regional blood flows were studied in two groups of 8 normotensive anaesthetized rabbits pretreated 24 h before the acute experiment either by substituting 0.45% NaCl for drinking water or with a subcutaneous injection of 20 mg kg-1 furosemide. Under barbiturate anaesthesia, regional blood flows were then measured with microspheres before and after i.v. administration of two doses of spirapril. With anaesthesia and surgery, plasma renin activity (PRA) was elevated in the salt-replete group and very high in the salt-depleted group (37 and 152 ng ml-1 h-1, respectively). Spirapril lowered blood pressure more in salt-depleted animals and increased only cardiac output and renal blood flow in salt-replete ones. Weak cardiodepression, associated with a small fall of cardiac output, was found in salt-depleted rabbits, indicating that very high angiotensin II levels may contribute to maintain cardiac function in volume-depleted animals with an activated sympathetic system. Coronary and skin blood flow decreased, and pancreatic and hepatic artery flow increased only in this group. A change in the salt balance can thus cause major differences in the responses of the peripheral circulation to angiotensin converting enzyme inhibition.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D011355:Prodrugs / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012964:Sodium / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011355:Prodrugs; D004656:Enalapril; C052555:spirapril; D012964:Sodium