Effect of prolonged treatment with amlodipine on enhanced vascular contractility in cardiomyopathic hamsters

This study examined the effects of prolonged treatment with amlodipine on t he enhanced vascular contractions in dilated cardiomyopathic (CM) hamsters. From the ages of 5 to 20 weeks, CM hamsters (BIO 53.58) orally received am lodipine. Then we compared the contractile responses to vasoconstrictors in aortas and mesenteric arteries from Chi hamsters with or without treatment with those in the arteries from controls (Flb). We also investigated the e ffect of amlodipine treatment on the Ca2+ sensitivity of tension in beta-es cin-skinned smooth muscle of mesenteric artery. The contractile responses t o phenylephrine, angiotensin II, and high K+ in both aorta and mesenteric a rtery were greatly enhanced in CM hamsters compared with controls. Amlodipi ne treatment slightly but significantly inhibited the enhanced responses in aorta but did not alter the responses in mesenteric arteries. The Ca2+ sen sitivity of tension was significantly increased in CM hamster preparations, which was unaffected by amlodipine treatment. These data. indicate that am lodipine treatment differentially affects the enhanced responses to vasocon strictors between large and small blood vessels from CM hamsters. The lack of effect of amlodipine treatment on the responsiveness of CM mesenteric ar tery leads to the suggestion that the preventive effect of amlodipine on fo cal myocytolytic necrosis of cardiomyocytes, which was previously reported to be the main cause of cardiomyopathy, results from an action on cardiomyo cytes.