Comparison of inhibitory effects of Y-27632, a Rho kinase inhibitor, in strips of small and large mesenteric arteries from spontaneously hypertensive and normotensive Wistar-Kyoto rats.
Since Y-27632, a specific inhibitor of Rho kinase, decreases the blood pressure in spontaneously hypertensive rats (SHR), it is suggested that Rho kinase is involved in the pathophysiology of hypertension. However, the effects of Y-27632 on isolated resistance arteries have never been determined. This study aimed to examine the possible role of the Rho/Rho kinase pathway during arterial contraction in isolated resistance arteries from SHR. The profile of arterial relaxant effects of Y-27632 was compared in endothelium-denuded strips of small and large mesenteric arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). The addition of 10(-6) mol/l norepinephrine (NE) to the strips of small arteries caused an initial peak followed by a tonic contraction in both strains. There was no difference between the two strains in either the initial peak or the tonic contraction. The addition of Y-27632 (0.3-3 micromol/l) to the tonic contraction of these strips caused a concentration-dependent relaxation in both strains. The relaxation was greater in SHR than in WKY. Similar results were observed in strips of large arteries. The relaxant effects of Y-27632 were greater in the large artery than in the small artery. Y-27632 also induced a concentration-dependent relaxation in strips precontracted with 65.9 mmol/l K+ depolarization. In both arteries, this relaxation was greater in SHR. The relaxant effects of Y-27632 were greater in the K+-contracted strips than in the NE-contracted strips. We conclude that Y-27632 shows the greater relaxant effects on the SHR arteries, and the effects are more evident in the large artery and in the K+-contracted strips.
Asano
Masahisa
M
Department of Cellular and Molecular Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan. masano@med.nagoya-cu.ac.jp
Nomura
Yukiko
Y
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D054460:rho-Associated Kinases
D000577:Amides; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D014662:Vasoconstrictor Agents; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009543:Nifedipine; D009638:Norepinephrine