Long-lasting cyclic guanosine-3 ',5 '-monophosphate accumulation in the medium of cultured smooth muscle cells from atherosclerotic rabbit aortas in response to exogenous or endogenous nitric oxide

Although atherosclerosis causes a marked inhibition of the endothelium-depe ndent vasorelaxation it also leads to expression of inducible nitric oxide synthase (iNOS), accompanied by an increase in cyclic GMP content, in the a rterial wall. The aim of our present study was to evaluate the influence of atherosclerosis on the soluble guanylyl cyclase pathway in Viable cultured smooth muscle cells (SMC) from rabbit atherosclerotic rabbit aortas (ather osclerotic SMC) and from control rabbit aortas (control SMC). In response t o 100 muM sodium nitroprusside (SNP), the intracellular production of cycli c GMP was similar in both types of cells, reaching a maximum after 5 min of incubation. In the culture medium, SNP evokes an increased cyclic GMP conc entration lasting 6 h in control SMC and 24 h in atherosclerotic SMC. Inter leukin-1 beta (100 IU/mL), which induces iNOS in SMC from both control and atherosclerotic aortas causes accumulation of cyclic GMP in the extracellul ar medium between 3 and 6 h for control SMC and between 3 and 24 h with ath erosclerotic SMC. These results demonstrate a long-lasting egression of cyc lic GMP in the extracellular medium of cultured SMC from rabbit aortas in r esponse to endogenous or exogenous NO. Since this egression of cyclic GMP l asts longer in atherosclerotic than in control SMC. we suggest that atheros clerosis dysregulates the long-term soluble quanylyl cyclase response to NO in SMC. (C) 2000 Editions scientifiques et medicales Elsevier SAS.