The study by Stamler et al. investigates the synthesis and characterization of biologically active compounds formed when nitric oxide (NO) reacts with protein thiol groups to form S-nitrosothiols. The authors demonstrate that under physiological conditions, NO can react with protein thiol groups to form S-nitroso proteins, which exhibit vasodilatory and antiplatelet properties similar to those of endothelium-derived relaxing factor (EDRF). These S-nitroso proteins are more stable than free NO, with a half-life of about 24 hours in physiological buffer and 40 minutes in plasma. The bioassays show that S-nitroso proteins induce persistent vasorelaxation and inhibit platelet aggregation, mediated by activation of guanylate cyclase and production of cyclic guanosine monophosphate (cGMP). The study suggests that S-nitrosothiol groups in proteins may serve as intermediates in the cellular metabolism of NO, providing a potential regulatory mechanism for NO activity. The findings highlight the importance of S-nitrosothiols in the biochemical mechanism of endogenously derived NO and their potential roles in physiological processes.The study by Stamler et al. investigates the synthesis and characterization of biologically active compounds formed when nitric oxide (NO) reacts with protein thiol groups to form S-nitrosothiols. The authors demonstrate that under physiological conditions, NO can react with protein thiol groups to form S-nitroso proteins, which exhibit vasodilatory and antiplatelet properties similar to those of endothelium-derived relaxing factor (EDRF). These S-nitroso proteins are more stable than free NO, with a half-life of about 24 hours in physiological buffer and 40 minutes in plasma. The bioassays show that S-nitroso proteins induce persistent vasorelaxation and inhibit platelet aggregation, mediated by activation of guanylate cyclase and production of cyclic guanosine monophosphate (cGMP). The study suggests that S-nitrosothiol groups in proteins may serve as intermediates in the cellular metabolism of NO, providing a potential regulatory mechanism for NO activity. The findings highlight the importance of S-nitrosothiols in the biochemical mechanism of endogenously derived NO and their potential roles in physiological processes.