ALTERED RESPONSIVENESS OF GUANYLYL CYCLASE TO NITRIC-OXIDE FOLLOWING TREATMENT OF CARDIOMYOCYTES WITH S-NITROSO-D,L-ACETYLPENICILLAMINE ANDSODIUM-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 sodiu m nitroprusside (SNP). Short- (2-hr) and long-term (24-hr) exposure at tenuated the maximal stimulation of GC by either SNAP or SNP by up to 80% (''desensitization''). However this ''desensitization'' of the myo cardial 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, The re was also evidence of ''cross-desensitization'' of GC (e.g., SNAP ex posure 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.