PHARMACOLOGICAL EFFECTS OF GEMFIBROZIL ON SOME CARDIOVASCULAR PREPARATIONS OF EXPERIMENTAL ANIMALS

Gemfibrozil (member of fibrates) is Peroxisome proliferator activated receptors (PPAR-α) agonist which improves lipid profiles particulary very low density lipoprotein and high density lipoprotein in patients with dyslipidemia.Objective: Studying the pharmacological effects of Gemfibrozil on some cardiovascular preparations of experimental animals. Materials and Methods: The experiments were conducted to study the effect of different doses of gemfibrozil on isolated perfused rabbit heart & coronary flow, isolated rabbit aortic spiral strip and mean arterial blood pressure of anaesthetized cats. Each experiment was done on six preparations. Results: In-vitro study: onisolated perfused rabbit heart, gemfibrozil (25-800µg/ml) produced a dose-dependent reduction on the amplitude of myocardial contractions. The inhibitory effect of gemfibrozil (100µg/ml) was not abolished after complete blockade of nicotinic and muscarinic receptors while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of calcium gluconate, isoprenaline, histamine and serotonin were not abolished after administration of gemfibrozil (100µg/ml). On coronary flow of isolated perfused rabbit heart, gemfibrozil (25-800μg/ml) produced also a dose-dependent reduction of  coronary flow. On isolated spiral aortic strips of rabbit , gemfibrozil produced dose-dependent significant reduction on nor-epinpherine (NE) induced contraction. In-vivo study gemfibrozil produced a dose-dependent significant reduction in mean arterial blood pressure (MABP) of anaesthetized cats. Conclusion: Gemfibrozil produced a negative inotropic effect through nitric oxide release  with a decrease in coronary flow. It also  reduced NE- induced contractions of aortic spiral strips with reduction in mean arterial blood pressure. So it must me used cauciously in cases of heart failure, but it could be  beneficial  in hypertensive patient with atherosclerosis.