Comparative effects of exogenous nitrovasodilators on cGMP levels in different canine blood vessels.
Nitrovasodilators, by releasing nitric oxide (NO) in vascular smooth muscle, activate soluble guanylate cyclase (sGC) in vascular smooth muscle. However, there is little information on their relative effectiveness, concentration ranges, or on the incubation times required to produce maximum sGC stimulation. To determine the optimal concentrations and 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 canine 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 respectively. Results indicate that cGMP levels vary with concentration of nitrovasodilators and time of incubation. SNAP was the least effective 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.
Bina
S
S
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 82014.
Hart
J L
JL
Muldoon
S M
SM
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000196:embryology*; D009569:Nitric Oxide / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D026403:S-Nitrosothiols; D014665:Vasodilator Agents / Q000494:pharmacology*
D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; C021315:S-nitrosocysteine; D010396:Penicillamine; D006152:Cyclic GMP; D003545:Cysteine