Antiischemic properties of fasudil in experimental models of vasospastic angina

We studied the antiisehemic properties of fasudil, a Rho-kinase inhibitor, in conscious rabbits with coronary vasospasm induced by vasopressin and end othelin. 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 ar terial strips. Fasudil and hydroxy fasudil significantly prevented the redu ction in coronary flow by vasopressin in the Langendorff perfused rat heart . Fasudil was effective in protecting the heart against vasopressin and end othelin-induced myocardial ischemic change in conscious rabbits, and this b eneficial effect can be attributed to its action of ameliorating the severe contraction of arteries. The inhibition of Rho-kinase may have implication s for the development of novel therapeutic strategies for vasospastic angin a in patients.