[Nitric oxide dependence of the anti-thrombotic effect of sydnonimines in coronary arteries of swine].
The metabolites of sydnonimine-derivatives generate nitric oxide (NO) and inhibit, like NO, platelet aggregation and adhesion. The purpose of the present study in anesthetized pigs was to examine if sufficient NO is generated by 3 sydnonimine-derivatives in vivo in order to prevent platelet-dependent arterial thrombosis. Stenosis of mechanically damaged coronary arteries resulted in cyclical blood flow reductions due to recurrent formation and embolization of platelet-thrombi. Injection of molsidomine (0.3 mg/kg) significantly reduced the frequency of cyclical flow reductions by 66%: 1.8 +/- 0.8/30 min versus 5.3 +/- 0.5/30 min before injection (p less than 0.01, n = 6). Molsidomine decreased arterial blood pressure by 34 +/- 7 mmHg (systolic) and 23 +/- 6 mmHg (diastolic) in these animals. Two further sydnonimine-derivatives were studied at a dose with similar hemodynamic effects. The onset of action of CAS 936 (2 mg/kg) was slow as compared to molsidomine. Therefore, CAS 936 reduced the frequency of cyclical flow reductions by 29% in the first hour following injection, but by 50% (p less than 0.05, n = 7) during the second hour. The remaining flow cycles were very small (mean size reduction 88%). C 89-4095 (0.6 mg/kg) prevented cyclical flow reductions nearly completely (reduction by 93%, p less than 0.01, n = 6). The subsequent injection of oxyhemoglobin reinitiated cyclical flow reductions in all three treatment groups. The antihypertensive drug dihydralazine (0.25 mg/kg) reduced blood pressure in 6 pigs by 38 +/- 3 (systolic) and 35 +/- 5 (diastolic) mmHg but had no effect on the frequency of cyclical coronary flow reductions.(ABSTRACT TRUNCATED AT 250 WORDS)
Just
M
M
Pharmaforschung Cassella AG, Frankfurt/Main.
Schönafinger
K
K
Martorana
P A
PA
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D003328:Coronary Thrombosis / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D011355:Prodrugs / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine; D013558:Sydnones / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D011355:Prodrugs; D013558:Sydnones; D014665:Vasodilator Agents; D009569:Nitric Oxide
NO-Abhängigkeit der antithrombotischen Wirkung von Sydnoniminen in Koronararterien von Schweinen.