Aminophylline potentiates sodium nitroprusside-induced hypotension in the dog.
The biochemical mechanisms by which nitroso-vasodilators cause smooth muscle relaxation remain controversial. One theory states that the effects of nitroso-vasodilators are mediated by increased intracellular levels of cyclic GMP due to activation of guanylate cyclase. To test this hypothesis, the authors examined the effects of sodium nitroprusside (SNP) in anesthetized dogs with an without pretreatment with the phosphodiesterase inhibitor aminophylline. Aminophylline pretreatment resulted in a 2.8-fold potentiation of the hypotensive effects of a continuous infusion of SNP. Potentiation also was seen for the effects of SNP on stroke volume, heart rate, and plasma cyclic GMP levels. These results support the hypothesis that nitroso-vasodilators exert their effects via guanylate cyclase activation. The authors advise caution when vasodilator therapy with agents such as SNP, nitroglycerin, or hydralazine is instituted in patients receiving aminophylline and when aminophylline is either instituted or discontinued in patients on vasodilator therapy.
D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006152:Cyclic GMP / Q000097:blood / Q000502:physiology; D004285:Dogs; D004357:Drug Synergism; D005292:Ferricyanides / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D013806:Theophylline / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D005292:Ferricyanides; D009599:Nitroprusside; D000628:Aminophylline; D013806:Theophylline; D006152:Cyclic GMP