Effect of the molsidomine metabolite SIN-1 on coronary arteries and peripheral vessels of sheep with special reference to tolerance and endothelium.

In vitro experiments on rings from coronary arteries, femoral arteries, and femoral veins of sheep were performed, and cumulative concentration-relaxation responses were established for glyceryl trinitrate (GTN) and the molsidomine metabolite SIN-1. Paired preparations of control and deendothelialized coronary artery rings were used, and the vessels were precontracted with different agonists at a concentration that elicited 30% of maximal contractions (EC-30). In coronary arteries, the responses for GTN and SIN-1 on normal and deendothelialized preparations were not significantly different. In coronary arteries preincubated with 0.44 mM GTN or SIN-1 to study tolerance development, there was a significant loss of efficacy to the relaxant effect of GTN, whereas the effect SIN-1 was essentially maintained. Femoral arteries and veins were readily relaxed with GTN. and SIN-1. In veins relaxation in relation to resting tone was much more pronounced than in coronary or femoral arteries. In conclusion, the molsidomine metabolite SIN-1 is a potent coronary and venous vasodilator that does not induce tolerance.