A Study of Vascular Relaxation Mechanism of GS-389, a New Potent Vasodilator.
10.4070/kcj.1991.21.6.1111
- Author:
Myung Kul YUM
;
Ki Churl CHANG
;
Yong Soo YUN
- Publication Type:Original Article
- MeSH:
Acetylcholine;
Animals;
Aorta;
Aorta, Thoracic;
Caffeine;
Cyclic GMP;
Endothelium;
Hydrolysis;
Isoproterenol;
Methylene Blue;
Mice;
Nitroprusside;
Phenylephrine;
Rats;
Relaxation*;
Vasodilation
- From:Korean Circulation Journal
1991;21(6):1111-1125
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
The mechanism of vasodilation effect of GS-389, 1-(4'-methoxybenzyl)-6,7 -dimethoxy-1,2,3,4-tetrhydroisoquinoline hydrocholoride, a possible cyclic GMP specific phosphodiesterase inhibitor, on rat and mouse thoracic aorta ring has been investigated. GS-389 relaxed rat and mouse thoracic aorta precontracted with phenylephrine and high K+(60mM) in concentration dependent manner. Presence or absence of endothelium did not alter the relaxing effects of it. GS-389 inhibited Ca2+-induced contraction of the high K+ or 1 uM phenylephrine. Initial phasic contraction induced by phenylephrine and caffeine in Ca2+ free solution was inhibited by GS-389. Methylene blue pretreatment suppressed relaxation effect of GS-389. Relaxation by isoproterenol or sodium nitroprusside and by acetylcholine in endotheilium preserved aorta was potentiated by concurrentadministration of GS-389. GS-389 inhibited phenylephrine-induced phosphatidylinositide hydrolysis. It is suggested that inhibition of phosphoinositide turnover associated with elevated cyclic nucleotide by GS-389 may be the possible vascular relaxation mechanism of it.
