COMPARATIVE EFFECTS OF EXOGENOUS NITROVASODILATORS ON CGMP LEVELS IN DIFFERENT CANINE BLOOD-VESSELS

Nitrovasodilators, by releasing nitric oxide (NO) in vascular smooth m uscle, activate soluble guanylate cyclase (sGC) in vascular smooth mus cle. However, there is little information on their relative effectiven ess, concentration ranges, or on the incubation times required to prod uce maximum sGC stimulation. To determine the optimal concentrations a nd incubation times we measured 3', 5'-cyclic guanosine monophosphate (cGMP) levels in response to different concentrations of NO, S-nitroso -L-cysteine (SNC), and S-nitroso-N-acetylpenicillamine (SNAP), in cani ne aorta, femoral, and carotid arteries incubated in Krebs. Production of cGMP following incubation of endothelium denuded tissues with NO, SNC, and SNAP peaked close to 20+/-5, 90+/-20, and 120+/-60 seconds re spectively. Results indicate that cGMP levels vary with concentration of nitrovasodilators and time of incubation. SNAP was the least effect ive in increasing cGMP levels among the three nitrovasodilators used. In different vascular beds, the production of cGMP in the presence of nitrovasodilators may depend on variations in the levels of guanylate triphosphate (GTP) and/or sGC.