Cardioprotective effect of hydroxyfasudil as a specific Rho-kinase inhibitor, on ischemia-reperfusion injury in canine coronary microvessels in vivo.
Rho-kinase modulates calcium sensitivity of the myosin light chain in smooth muscle cells and has been implicated as playing a pathogenetic role in cardiovascular disorders. This paper was aimed to determine whether hydroxyfasudil (a specific Rho-kinase inhibitor) exerts cardioprotective effect on coronary ischemia-reperfusion (I/R) injury, and if so, whether NO is involved. Canine subepicardial small arteries (diameter > or = 100 microm) and arterioles (diameter < 100 microm) were observed by a CCD intravital microscope during coronary I/R. Coronary vascular responses to endothelium-dependent (acetylcholine) and -independent (papaverine) vasodilators were examined after I/R under three conditions: control, preconditioning, and hydroxyfasudil. Coronary I/R significantly impaired coronary vasodilation to acetylcholine, whereas hydroxyfasudil completely preserved the responses, as did preconditioning. Hydroxyfasudil also significantly reduced myocardial infarct size. These results indicated that hydroxyfasudil exerts cardioprotective effects on coronary I/R injury in vivo, for which NO-mediated mechanism may be involved.
Department of Medical Engineering and Systems Cardiology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan. yada@me.kawasaki-m.ac.jp
Toyotaka
T
Yada
Hiroaki
H
Shimokawa
Fumihiko
F
Kajiya
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004791:Enzyme Inhibitors; D019157:Ischemic Preconditioning, Myocardial; D008833:Microcirculation / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009569:Nitric Oxide / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors*
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; C431085:hydroxyfasudil; D009569:Nitric Oxide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D020741:rho GTP-Binding Proteins