Korean Circ J.  1991 Dec;21(6):1111-1125. 10.4070/kcj.1991.21.6.1111.

A Study of Vascular Relaxation Mechanism of GS-389, a New Potent Vasodilator

• Yum MK
• Chang KC
• Yun YS

• KMID: 2228994
• DOI: http://doi.org/10.4070/kcj.1991.21.6.1111

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.

MeSH Terms

Acetylcholine
Animals
Aorta
Aorta, Thoracic
Caffeine
Cyclic GMP
Endothelium
Hydrolysis
Isoproterenol
Methylene Blue
Mice
Nitroprusside
Phenylephrine
Rats
Relaxation*
Vasodilation
Acetylcholine
Caffeine
Cyclic GMP
Isoproterenol
Methylene Blue
Nitroprusside
Phenylephrine