Altered responsiveness of guanylyl cyclase to nitric oxide following treatment of cardiomyocytes with S-nitroso-D,L-acetylpenicillamine and sodium nitroprusside

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,1-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. (C) 1997 Academic Press.