Antiischemic properties of fasudil in experimental models of vasospastic angina.
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.
Sato
S
S
Institute of Life Science Research, Asahi Kasei Corporation, Tagata-gun, Shizuoka, Japan. sato.sn@om.asahi-kasei.co.jp
Ikegaki
I
I
Asano
T
T
Shimokawa
H
H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000787:Angina Pectoris / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D003329:Coronary Vasospasm / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D016232:Endothelins / Q000008:administration & dosage; D006632:Histamine / Q000008:administration & dosage; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000008:administration & dosage; D054460:rho-Associated Kinases
D016232:Endothelins; D047908:Intracellular Signaling Peptides and Proteins; D014665:Vasodilator Agents; D014667:Vasopressins; D006632:Histamine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil