QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.108.148247v1 329/2/820    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chan, C. K. Y. Articles by Vanhoutte, P. M. Search for Related Content PubMed PubMed Citation Articles by Chan, C. K. Y. Articles by Vanhoutte, P. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines

CARDIOVASCULAR

Rho Kinase Inhibitors Prevent Endothelium-Dependent Contractions in the Rat Aorta

Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China (C.K.Y.C., J.C.M., R.Y.K.M., P.M.V.); and Department of Medicine, University of Hong Kong, Hong Kong, China (J.C.M.)

Rho kinase is involved in the pathogenesis of hypertension, which favors the occurrence of endothelium-dependent contractions. The present study was designed to determine the effects of two Rho kinase inhibitors, HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine (fasudil)] and Y27632 [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide dihydrochloride], on endothelium-dependent and -independent contractions. Isometric tension of 1-year-old spontaneously hypertensive rat and Wistar Kyoto aortae were measured. In the presence of N-nitro-L-arginine methyl ester, HA1077, and Y27632 reduced endothelium-dependent contractions caused by acetylcholine and the calcium ionophore 5-(methylamino)-2-[[2R,3R,6S,8S,9R,11R)-3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)-ethyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid (A23187). The Rho kinase inhibitors did not significantly affect prostacyclin production measured as 6-keto prostaglandin F₁. They nearly abolished endothelium-independent contractions to (5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2-oxabicyclo-[2.2.1]hept-5-yl]-5-heptenoic acid (U46619), prostaglandin F₂, and phenylephrine. Western blotting revealed a comparable expression of Rho kinase in the aortae of the two strains. The reduction by Rho kinase inhibitors of endothelium-dependent contractions is mainly because of their direct effect on the vascular smooth muscle cells.

Address correspondence to: Dr. Paul M. Vanhoutte, Department of Pharmacology, 2/F, Laboratory Block, Faculty of Medicine Bldg., 21 Sassoon Rd., Pokfulam, University of Hong Kong, Hong Kong, China. E-mail: vanhoutt{at}hku.hk