Relaxations to endothelium-derived relaxing factor and the metabolite of molsidomine, SIN-1, in the aorta and the hindquarters of the rat.
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.
Van de Voorde
J
J
Laboratory of Normal and Pathological Physiology, University of Gent, Belgium.
Claeys
M
M
Leusen
I
I
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001013:Aorta, Thoracic; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004730:Endothelium, Vascular / Q000187:drug effects*; D006614:Hindlimb / Q000098:blood supply; D006977:Hypertension, Renal / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects
D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D005996:Nitroglycerin