Effect of prolonged treatment with amlodipine on enhanced vascular contractility in cardiomyopathic hamsters.
This study examined the effects of prolonged treatment with amlodipine on the enhanced vascular contractions in dilated cardiomyopathic (CM) hamsters. From the ages of 5 to 20 weeks, CM hamsters (BIO 53.58) orally received amlodipine. Then we compared the contractile responses to vasoconstrictors in aortas and mesenteric arteries from CM hamsters with or without treatment with those in the arteries from controls (F1b). We also investigated the effect of amlodipine treatment on the Ca2+ sensitivity of tension in beta-escin-skinned smooth muscle of mesenteric artery. The contractile responses to phenylephrine, angiotensin II, and high K+ in both aorta and mesenteric artery were greatly enhanced in CM hamsters compared with controls. Amlodipine treatment slightly but significantly inhibited the enhanced responses in aorta but did not alter the responses in mesenteric arteries. The Ca2+ sensitivity of tension was significantly increased in CM hamster preparations, which was unaffected by amlodipine treatment. These data indicate that amlodipine treatment differentially affects the enhanced responses to vasoconstrictors between large and small blood vessels from CM hamsters. The lack of effect of amlodipine treatment on the responsiveness of CM mesenteric artery leads to the suggestion that the preventive effect of amlodipine on focal myocytolytic necrosis of cardiomyocytes, which was previously reported to be the main cause of cardiomyopathy, results from an action on cardiomyocytes.
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan. asato@med.hokudai.ac.jp
A
A
Sato
Y
Y
Hattori
M
M
Watanabe
H
H
Okamoto
H
H
Tomioka
M
M
Fukao
I
I
Sakuma
A
A
Kitabatake
M
M
Kanno
D008841:Actin Cytoskeleton / Q000502:physiology*; D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D009202:Cardiomyopathies / Q000188:drug therapy*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007537:Isometric Contraction; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D000804:Angiotensin II; D017311:Amlodipine; D010656:Phenylephrine; D011188:Potassium; D002118:Calcium