title: Effect of the molsidomine metabolite SIN-1 on coronary arteries and peripheral vessels of sheep with special reference to tolerance and endothelium.
abstract: 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.
authors.affiliation: Department of Pharmacology-Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
authors.forename: M H
authors.initials: MH
authors.lastname: Yousif
authors.forename: F
authors.initials: F
authors.lastname: Yousif
authors.forename: O
authors.initials: O
authors.lastname: Thulesius
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004727:Endothelium / Q000378:metabolism; D005263:Femoral Artery / Q000187:drug effects; D005268:Femoral Vein / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D005996:Nitroglycerin / Q000494:pharmacology; D012756:Sheep; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D005996:Nitroglycerin