Comparative cardiovascular effects of a novel angiotensin converting enzyme inhibitor altiopril calcium (MC-838) and captopril in spontaneously hypertensive rats.
The cardiovascular effects of a newly developed angiotensin converting enzyme (ACE) inhibitor, calcium(-)-N-[(S)-3-[(N-cyclohexylcarbonyl-D-alanyl)thio]-2- methylpropionyl]-L-prolinate (MC-838, altiopril calcium), were examined in anesthetized spontaneously hypertensive rats and isolated donor-perfused, rat heart preparations, and compared with those of captopril. Equidepressor doses of MC-838 (0.3 and 3 mg/kg) and captopril (0.03 and 0.3 mg/kg) given i.v. induced dose-dependent decreases in systemic blood pressure, left ventricular systolic pressure (LVSP), LVdP/dT max, and femoral, renal and mesenteric vascular resistance. MC-838 as well as captopril had no significant effects on femoral blood flow (except for 3 mg/kg MC-838) and heart rate (HR). Marked and sustained increases in renal blood flow were observed with the ACE inhibitors. These agents caused two-phase changes in mesenteric blood flow: initial increase followed by decrease. In isolated, donor-perfused rat heart preparations, MC-838 (0.01-1 mg) injected locally into the coronary artery resulted in positive inotropic effects, as indicated by dose-dependent increases in LVSP and LVdP/dT max, with no significant changes in HR, while captopril (0.01-1 mg) had negative inotropic effects. The positive inotropic response to MC-838 appears to be due to Ca++ in the MC-838 solution.
Akima
M
M
Department of Pharmacology, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Shiraki
Y
Y
Sakai
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; C048961:MC 838; D011392:Proline; D002216:Captopril