Experimental studies on the mechanism of glyceryl trinitrate-tolerance and dependence.
Tolerance to glyceryl-trinitrate (GTN) in arteries and veins was studied in different in vitro and in vivo models. The development of GTN tolerance was associated with a down-regulation of the cGMP system, i.e. an impairment of the nitrocompound-dependent activation of guanylate cyclase and an increase of the cGMP-phosphodiesterase activity. We suggest that a decreased function of the cGMP system might cause an impairment of the negative feedback loop involving cGMP in blood vessels, and a concomitant supersensitivity to contractile stimuli.
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism; D004361:Drug Tolerance; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D014664:Vasodilation / Q000187:drug effects*
D005996:Nitroglycerin; D006152:Cyclic GMP