An investigation into the mechanism of action of nitroprusside on isolated cardiovascular tissues
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The effect of photolysis of nitroprusside was investigated in both frog ventricular trabeculae and rabbit ear arterial strips. Unphotolysed nitroprusside failed to elicit any effect on frog ventricular twitch tension. However, upon photolysis it had a potent negative inotropic action. The extent of twitch depression was shown to depend on the degree of photolysis. It was postulated that these effects are due to a labile physiologically active photolytic product. This was positively identified as nitric oxide. Preliminary results of the negative inotropic action of thiols and synthesised nitrosothiols are also presented. In contrast to frog ventricle, intact nitroprusside does exert a relaxing effect on precontracted mammalian smooth muscle. This effect is markedly potentiated by photolysis. It is concluded that the mechanism of action of nitroprusside on both tissues involves the release of nitric oxide which is postulated to activate guanylate cyclase. This suggests that mammalian vascular smooth muscle has a mechanism for degrading nitroprusside which is absent in frog ventricle.
Thesis, PhD Doctor of Philosophy