Exogenous GTP enhances the effects of sodium nitrite on cyclic GMP accumulation, vascular smooth muscle relaxation and platelet aggregation.
Exogenous guanosine triphosphate (GTP) (1-2 x 10(-4)M) resulted in increased concentrations of cyclic GMP both in endothelium denuded rat mesenteric artery (RMA) and in human ADP-stimulated platelets. Sodium nitrite (3.3 x 10(-4)M) relaxed precontracted RMA by 34%. When the arteries were preincubated with GTP (2 x 10(-4)M) sodium nitrite administration resulted in a significantly greater relaxation (58%) of the RMA with concomitant 2-fold increase in cGMP. Sodium nitrite (1 x 10(-4)M) had an inhibitory effect on ADP-induced platelet aggregation. Preincubation with GTP enhanced significantly the sodium nitrite-induced inhibition of ADP-induced platelet aggregation with a simultaneous 5-fold increase in cGMP. These results indicate that exogenous GTP enhances the sodium nitrite-induced stimulation of guanylate cyclase and thus enhances the effects of sodium nitrite on arterial smooth muscle and platelets.
Laustiola
K E
KE
Wihuri Research Institute, Kalliolinnantie 14, Helsinki, Finland.
Vuorinen
P
P
Pörsti
I
I
Metsä-Ketelä
T
T
Manninen
V
V
Vapaatalo
H
H
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004357:Drug Synergism; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012977:Sodium Nitrite / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D010975:Platelet Aggregation Inhibitors; D006160:Guanosine Triphosphate; D006152:Cyclic GMP; D012977:Sodium Nitrite