NITROGLYCERIN TOLERANCE AND CYCLIC-GMP GENERATION IN THE LONGITUDINAL SMOOTH-MUSCLE OF THE GUINEA-PIG ILEUM

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 225  (1) , 29-34
Abstract
The effects of in vitro nitroglycerin [a vasodilator] tolerance and methylene blue pretreatment on the ability of nitroglycerin and nitroprusside to promote relaxation and tissue accumulation of cGMP were examined in the carbachol-contracted longitudinal smooth muscle of the guinea-pig ileum. Nitroglycerin and nitroprusside produced concentration-dependent increases in cGMP levels. Only nitroglycerin increased cGMP levels before the onset of relaxation. Nitroglycerin tolerance produced approximately 200- and 5-fold shifts to the right of nitroglycerin and nitroprusside relaxation curves, respectively. Methylene blue pretreatment produced approximately 5-fold shifts to the right of both nitroglycerin and nitroprusside relaxation curves. Whenever there was an inhibition of nitroglycerin- or nitroprusside-induced relaxation, there was a corresponding reduction of cGMP generation. Methylene blue inhibited the ability of 8-bromoGMP to promote smooth muscle relaxation, suggesting that it also may impair the subsequent actions of cGMP. This study provides the 1st demonstration of nitroglycerin tolerance in a nonvascular smooth muscle and provides evidence that cGMP mediates the relaxant effects of nitroglycerin in the longitudinal smooth muscle of the guinea pig ileum. However, because nitroprusside promoted tissue accumulation of cGMP subsequent to relaxation, an exclusive role for cGMP-mediated relaxation for this drug in the longitudinal smooth muscle appears unlikely.