Sodium nitroprusside, an endothelium-derived relaxing factor congener, increases platelet cyclic GMP levels and inhibits epinephrine-exacerbated in vivo platelet thrombus formation in stenosed canine coronary arteries.
Sodium nitroprusside (SNP), a nitrosovasodilator, increases platelet cyclic GMP levels and inhibits platelet activity in vitro. The antiplatelet properties of SNP are not well established in vivo, however, and consequently are not appreciated by clinicians. In our established model of mechanically stenosed canine coronary arteries (MSCA) with intimal damage, periodic acute platelet thrombus formation (APTF) occurs, followed by embolization distally, which then causes cyclic flow reductions (CFRs) in coronary blood flow. Aspirin (ASA) abolished platelet-mediated CFRs in our model, but they recur when epinephrine (EPI) is infused (0.2 microgram/kg/min). SNP was given continuously intravenously (i.v.) to 17 dogs with MSCA; CFRs were abolished in all dogs by SNP at 4.4 +/- 2.7 micrograms/kg/min (mean +/- SD). Mean arterial blood pressure (MAP) decreased by 19 +/- 9 mm Hg (p < 0.001) from control, while heart rate (HR) increased 35 +/- 20 beats/min (p < 0.001). Platelet cyclic GMP levels were 2.9 +/- 1.1 pmol/10(8) platelets before SNP infusion, and increased to 4.3 +/- 1.6 pmol/10(8) platelets (p < 0.05) when CFRs were abolished. CFRs were not renewed during the continued SNP infusion when EPI was infused at 0.2 microgram/kg/min for 20 min in 11 dogs, but CFRs returned within 5-25 min after the SNP infusion was terminated. The return of CFRs occurred together with a decrease in platelet cyclic GMP levels to 3.3 +/- 1.4 pmol/10(8) platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
Rovin
J D
JD
Department of Medicine, University of Wisconsin Medical School, Madison 53792.
Stamler
J S
JS
Loscalzo
J
J
Folts
J D
JD
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D003328:Coronary Thrombosis / Q000188:drug therapy*; D006152:Cyclic GMP / Q000097:blood*; D004195:Disease Models, Animal; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D009599:Nitroprusside; D006152:Cyclic GMP; D001241:Aspirin; D004837:Epinephrine