Regional haemodynamic effects of captopril, enalaprilat and lisinopril in conscious water-replete and water-deprived Brattleboro rats.
1. The regional haemodynamic effects of intravenous bolus doses of captopril, enalaprilat and lisinopril were assessed in conscious Brattleboro (i.e. vasopressin-deficient) rats, chronically instrumented with miniaturized pulsed Doppler probes and intravascular catheters. 2. Responses to incremental doses of each drug (spanning the median effective dose for the inhibition of the pressor response to angiotensin I) were examined in both water-replete and water-deprived states. 3. In the water-replete state, the haemodynamic profiles of captopril, enalaprilat and lisinopril were generally similar, with incremental doses causing rises in mesenteric and renal flow and, to a lesser extent, hindquarters flow. There were small tachycardias and only slight falls in mean blood pressure. 4. In the water-deprived state, the effects of all three drugs were greatly enhanced; tachycardic and hypotensive effects occurred together with increases in mesenteric, renal and hindquarters flows. However, for renal flow and renal vascular conductance the effectiveness of the drugs decreased in the order enalaprilat greater than captopril greater than lisinopril, whereas for mesenteric flow and mesenteric vascular conductance the order was captopril greater than enalaprilat greater than lisinopril. 5. Since marked haemodynamic actions were seen with doses one-tenth of the median effective dose for the inhibition of the pressor effect of angiotensin I, it is likely these effects were due to inhibition of angiotensin-converting enzyme, although not necessarily to inhibition of angiotensin II production.(ABSTRACT TRUNCATED AT 250 WORDS)
Muller
A F
AF
Department of Medicine, University Hospital, Nottingham, U.K.
Gardiner
S M
SM
Compton
A M
AM
Bennett
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000031:analogs & derivatives* / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D017706:Lisinopril; D008297:Male; D051381:Rats; D011910:Rats, Brattleboro; D012039:Regional Blood Flow / Q000187:drug effects; D014868:Water Deprivation / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D002216:Captopril; D017706:Lisinopril; D015773:Enalaprilat