Shin-ichi Satoh1,*, Ichiro Ikegaki1, Toshio Asano1 and Hiroaki Shimokawa2
1Institute of Life Science Research, Asahi Kasei Corporation, 632-1, Mifuku, Ohito-cho, Tagata-gun, Shizuoka 410-2321, Japan
2Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
*Corresponding author. FAX: +81-558-76-7147, E-mail: sato.sn@om.asahi-kasei.co.jp
Abstract: We studied the antiischemic properties of fasudil, a Rho-kinase inhibitor, in conscious rabbits with coronary vasospasm induced by vasopressin and endothelin. Pretreatment with fasudil (0.3 and 3 mg/kg) attenuated the maximum elevation of the T-wave elicited by endothelin. Pretreatment with fasudil inhibited the T-wave elevation elicited by vasopressin. Fasudil and hydroxy fasudil, an active metabolite of fasudil, relaxed the endothelin-, U-46619-, 5-hydroxytryptamine- or histamine-induced contraction in swine coronary arterial strips. Fasudil and hydroxy fasudil significantly prevented the reduction in coronary flow by vasopressin in the Langendorff perfused rat heart. Fasudil was effective in protecting the heart against vasopressin and endothelin-induced myocardial ischemic change in conscious rabbits, and this beneficial effect can be attributed to its action of ameliorating the severe contraction of arteries. The inhibition of Rho-kinase may have implications for the development of novel therapeutic strategies for vasospastic angina in patients.
Keywords: Coronary vasospasm, Angina, Rho-kinase inhibitor, Fasudil, Hydroxy fasudil
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