Long-lasting ex vivo inhibition by perindopril of rat vascular response to angiotensin I.
The ex vivo effects of perindopril and enalapril, inhibitors of angiotensin-converting enzyme (ACE), were studied on rat aortae and perfused hearts to clarify the inhibition of vascular response to angiotensin I. The duration of the effects of these inhibitors was also studied. One hour after oral administration of perindopril (0.1-30 mg/kg) or enalapril (0.3-100 mg/kg), the aortae and hearts were isolated for the measurement of isometric force and coronary flow, respectively. In aortae, perindopril and enalapril dose-dependently inhibited the maximal contractions to angiotensin I (1-1000 nM). In isolated perfused hearts, the compounds inhibited the decrease in coronary flow induced by angiotensin I (100 ng). In other experiments, the inhibitory effects of perindopril lasted for 24 h in both aortae (3 mg/kg, p.o.) and hearts (10 mg/kg, p.o.). In contrast, the effects of enalapril disappeared within 6 h in aortae (3 mg/kg, p.o.) and 12 h in hearts (100 mg/kg, p.o.). These results demonstrate that oral administration of ACE inhibitors reduce the ex vivo vascular response to angiotensin I and suggest that perindopril is a longer-lasting inhibitor than enalapril on vascular contraction to locally generated angiotensin II.
Ishigai
Y
Y
Exploratory Research Laboratories II, Tokyo R&D Center, Daiichi Pharmaceutical Co., Ltd., Japan.
Fukuzawa
A
A
Chiba
K
K
Irie
K
K
Shibano
T
T
D000284:Administration, Oral; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D020913:Perindopril; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D004656:Enalapril; D000803:Angiotensin I; D020913:Perindopril