Coronary effects of cyclovirobuxine D in anesthetized pigs and in isolated porcine coronary arteries.
The present study was undertaken in anesthetized pigs and in isolated porcine coronary arteries to determine the primary coronary effects of cyclovirobuxine D. In six pigs, the intravenous administration of 1.5 mg/kg of cyclovirobuxine D whilst preventing changes in heart rate and aortic blood pressure caused increases in left ventricular dP/dtmax and coronary blood flow which 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 pigs). Intravenous blockade of nitric oxide synthase (L-NAME, five pigs) abolished both responses, while intracoronary injection of L-NAME (five pigs) abolished 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 cyclooxygenase with indomethacin (five segments) or potassium channels blockade with glibenclamide (five segments), but it was abolished by L-NAME (five segments) 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 oxide.
Grossini
E
E
Dipartimento di Scienze Mediche, Facoltà di Medicina e Chirurgia, Università del Piemonte Orientale A. Avogadro, Novara, Italy. grossini@scimed1.med.no.unipmn.it
Battaglia
A
A
Brunelleschi
S
S
Mary
D A
DA
Molinari
C
C
Viano
I
I
Vacca
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D002317:Cardiovascular Agents; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; C032939:cyclovirobuxine D; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester