Eucalyptol potentiates antianginal effect while blunts tachycardia of nifedipine in rats via nitric oxide, antioxidant, and anti-inflammatory pathways: In vivo and in vitro study

Eucalyptol; a terpenoid oxide present in numerous plant-derived essential oils; is used in many foodstuffs, however, its excessive use can cause serious adverse effects. This study investigated effects of the lowest effective doses of eucalyptol in vasopressin-induced ischemia in rats which simulates human angina. In vivo evaluations included ECG, blood pressure, plasma nitric oxide (NO), aortic endothelial NO synthase (eNOS) mRNA expression, and myocardial oxidative and inflammatory markers. In vitro experiments were performed in isolated aortic and heart preparations. Eucalyptol improved angina manifestations, coronary flow, plasma NO, and aortic eNOS mRNA expression. It inhibited phenylephrine-induced contractions of endothelium-intact rings. Its relaxant effects decreased in L-NAME-pretreated rings and endothelium-denuded rings. Combination of eucalyptol and nifedipine exerted significant effects larger than each compound alone with blunting of nifedipine-induced tachycardia. The vascular eNO, antioxidant, and anti-inflammatory pathways were involved. This could lead to the development of a therapeutic antianginal system of both compounds.