Relaxations to endothelium-derived relaxing factor and the metabolite of molsidomine, SIN-1, in the aorta and the hindquarters of the rat

• Published in: Journal of cardiovascular pharmacology Vol. 14 Suppl 11; p. S55
• Main Authors: Van de Voorde, J, Claeys, M, Leusen, I
• Format: Journal Article
• Language: English
• Published: United States 1989
• Subjects: Animals; Aorta - drug effects; Aorta, Thoracic; Dose-Response Relationship, Drug; Drug Tolerance; Endothelium, Vascular - drug effects; Hindlimb - blood supply; Hypertension, Renal - physiopathology; Hypertension, Renovascular - physiopathology; In Vitro Techniques; Male; Molsidomine - administration & dosage; Molsidomine - analogs & derivatives; Molsidomine - pharmacology; Nitric Oxide - administration & dosage; Nitric Oxide - pharmacology; Nitroglycerin - administration & dosage; Nitroglycerin - pharmacology; Rats; Rats, Inbred Strains; Vascular Resistance - drug effects
• ISSN: 0160-2446
• DOI: 10.1097/00005344-198906152-00010

The effects of SIN-1 were studied on isolated aortic rings and perfused hindquarters of the rat and were compared with the effects of nitroglycerin and endothelium-derived relaxing factor (EDRF) released by acetylcholine or histamine (aorta) and carbachol (hindquarters). SIN-1 relaxes rat aortic rings in a dose-dependent and endothelium-independent way. Aortic rings made tolerant to nitroglycerin in vitro show cross-tolerance to isosorbide dinitrate but no cross-tolerance to EDRF, sodium nitroprusside, or SIN-1. Aortic rings made tolerant to nitroglycerin by in vivo treatment show an important cross-tolerance to isosorbide dinitrate, a small degree of tolerance to sodium nitroprusside, but no significant tolerance to SIN-1 or EDRF. Also, in the nitroglycerin-tolerant hindquarter vasculature, no cross-tolerance is found to EDRF or SIN-1. In the aorta of renal hypertensive rats, in which the relaxation to EDRF-dependent dilators is impaired, no depression of the maximal response to SIN-1 occurs.