Altered Responsiveness of Guanylyl Cyclase to Nitric Oxide Following Treatment of Cardiomyocytes withS-Nitroso-d,l-acetylpenicillamine and Sodium Nitroprusside☆

Abstract The stimulation of cardiomyocyte guanylyl cyclase by nitric oxide (NO)-donor drugs was examined before and after exposure of these cells to the NO-donor drugs: S-nitroso-d,l-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP). Short- (2-hr) and long-term (24-hr) exposure attenuated the maximal stimulation of GC by either SNAP or SNP by up to 80% (“desensitization”). However this “desensitization” of the myocardial GC was atypical in nature in that the reduction in maximal NO-stimulated GC activity was associated with an increase in the affinity of the GC towards either NO-donor, a finding not as yet reported. There was also evidence of “cross-desensitization” of GC (e.g., SNAP exposure decreasing the stimulatory effect of SNP). Further, this is the first time that SNAP-induced desensitization of GC has been observed.