Long-term inhibition of angiotensin converting enzyme suppresses calcium channel agonist-induced contraction of aorta in hypertensive rats.
To elucidate functional changes in the vascular smooth muscle of spontaneously hypertensive rats (SHR) after chronic inhibition of angiotensin converting enzyme, we examined the contractile responses to different pharmacological interventions in the isolated aortas from SHR treated with a novel angiotensin converting enzyme inhibitor, CS-622 (10 mg/kg/day) for 20 weeks. In normal K+ medium, a marked contraction was elicited by increasing Ca2+ concentration from 0 to 3 mM in aortas from a control group of SHR, but not in aortas from SHR treated with CS-622. In 60 mM K+ medium, however, the sensitivity of aorta to Ca2+ was almost the same in the two groups. A calcium channel activator, CGP-28392 (10(-7) to 10(-6) M), induced a marked contraction in the aortas from control SHR, but not in the aortas from CS-622-treated SHR. When slightly depolarized in 10 or 12 mM K+ solution, the aortas from CS-622-treated SHR contracted in response to CGP-28392. The aortic sensitivity to KCl contraction was much lower in CS-622-treated SHR than in untreated SHR, whereas the sensitivity to phenylephrine contraction was little different in the two groups. These contractile profiles of aortas from CS-622-treated SHR were very similar to those from normotensive Wistar-Kyoto rats but not to those from hydralazine-treated SHR. These data suggest that contractions due to Ca2+ through voltage-dependent calcium channels are exaggerated in SHR aorta and that long-term treatment with angiotensin converting enzyme inhibitor suppresses the abnormal contractility of SHR vascular smooth muscle, probably through alterations of voltage-related functions of calcium channels.
Sada
T
T
Cardiovascular Division, Sankyo Co., Ltd., Tokyo, Japan.
Koike
H
H
Miyamoto
M
M
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013841:Thiazepines / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D011725:Pyridines; D013841:Thiazepines; D010656:Phenylephrine; D006830:Hydralazine; D011189:Potassium Chloride; C040525:CGP 28392; C055603:temocapril hydrochloride; D002122:Calcium Chloride