Anti-ischemic actions of molsidomine by venous and large coronary dilatation in combination with antiplatelet effects.
Molsidomine and its vasoactive metabolite SIN-1 elicit anti-ischemic properties by a therapeutically useful pattern of different vasoactive actions combined with a cyclic GMP-mediated inhibition of platelet adhesion and aggregation. Following molsidomine or SIN-1, local venodilatation and an increase in total effective vascular compliance (as an integrated parameter of venodilatation) were observed. This reduction in preload caused a decrease in myocardial oxygen consumption. Molsidomine caused a slowly progressing dilatation (still present and significant after 4 h), while SIN-1 caused an immediate increase in diameter of the large coronary arteries. The cyclic GMP-mediated dilator effects were accompanied by similar increases in platelet cyclic GMP levels (in the effluent of perfused hearts), indicating an increased potential against platelet activation, adhesion, and aggregation. The combined effect on cardiac preload, conductance of the epicardial arteries, and inhibition of platelet activation improves the ratio between myocardial oxygen supply and demand and suppression of ischemic events.
Bassenge
E
E
Institute of Applied Physiology, University of Freiburg, F.R.G.
Mülsch
A
A
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D003331:Coronary Vessels / Q000187:drug effects*; D006152:Cyclic GMP / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; C002385:linsidomine; D008981:Molsidomine; D006152:Cyclic GMP