Experimental studies on the mechanism of glyceryl trinitrate-tolerance and dependence
Axelsson, K.L.; Ahlner, J.; Areskog, N.H.; Andersson, R.G.
Zeitschrift für Kardiologie 75(Suppl 3): 28-29
1986
ISSN/ISBN: 0300-5860 PMID: 3026103 Document Number: 284856
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.