Coronary effects of cyclovirobuxine D in anesthetized pigs and in isolatedporcine coronary arteries

The present study was undertaken in anesthetized pigs and in isolated porci ne coronary arteries to determine the primary coronary effects of cycloviro buxine D. In six pigs, the intavenous administration of 1.5 mg/kg of cyclov irobuxine D whilst preventing changes in heart rate and aortic blood pressu re caused increases in left ventricular dP/dtmax and coronary blood flow wh ich respectively averaged 10% and 23.9%. These responses were progressively augmented by graded increases in the dose of the drug (four pigs) and were not affected by blockade of cholinergic and adrenergic receptors (five pig s). Intravenous blockade of nitric oxide synthase (L-NAME, five pigs) aboli shed both responses, while intracoronary injection of L-NAME (five pigs) ab olished only the coronary vasodilatation. In ten isolated coronary segments , cyclovirobuxine D significantly reduced the degree of potassium chloride- induced contraction. This reduction was not affected by inhibition of cyclo oxygenase with indomethacin (five segments) or potassium channels blockade with glibenclamide (five segments), but it was abolished by L-NAME (five se gments) or removal of endothelium (five segments). The present study showed that cyclovirobuxine D caused a primary effect of coronary vasodilatation, which involved mechanisms related to the endothelial release of nitric oxi de. (C) 1999 Elsevier Science Inc.