Mecanismos envolvidos no efeito cardiovascular induzido por (-)-mirtenol em ratos hipertensos e normotensos

Abstract

Cardiovascular diseases represent a serious public health problem, since they are the main cause of morbidity and mortality in the world. Hypertensive disease is the main cardiovascular disorder and it is estimated that 1.13 billion people have the pathology. The pharmacological treatment of hypertension has some limitations, such as the induction of tolerance and adverse effects, which favor the abandonment of treatment, only one in five hypertensive patients effectively control the disease. (-)-myrtenol, a monoterpene found in various essential oils of plants, induces anxiolytic, antioxidant, cardioprotective activity and can have antihypertensive effect, making it a future alternative for the treatment of hypertension. In this sense, the objective was to determine the mechanisms involved in the cardiovascular effect induced by (-)-myrtenol in hypertensive (SHR) and normotensive (NWR) animals. SHR and NWR animals from 12 - 14 weeks were used, the hemodynamic parameters of blood pressure (BP) and heart rate (HR) were measured after acute and intravenous administration of (-)-myrtenol. The influence of the substance on the autonomic control of cardiovascular function was evaluated with the use of hexamethonium. With the electrocardiogram, the electrical activity of the heart was evaluated after intravenous administration of (-)- mirtenol. The vasorelaxing effect on upper mesenteric artery rings was analyzed in an organ bath system isolated at 37 ° C. Intravenous administration of (-)-myrtenol triggered a dose-dependent hypotensive effect in SHR and NWR animals (p<0.05), with a greater effect in hypertensive animals. In SHR animals, the substance had a biphasic effect (p <0.05) or HR and in NWR animals, reflex tachycardia (p<0.05) occurred. In SHR, in the presence of the ganglionic blocker, hypotension increased at the lowest doses and decreased at the highest dose of (-)-myrtenol (p<0.05). In NWR animals there were no changes in the hypotensive effect in the presence of hexamethonium, only reflex tachycardia was inhibited (p<0.05). In SHR animals, the PRi, QRS and QTc intervals were prolonged (p <0.05) and the amplitude of the R wave reduced (p<0.05), and in NWR animals, only the amplitude of the R wave was reduced (p<0.05). Oral administration of (-) - mirtenol in SHR animals triggered a hypotensive effect after 10 minutes of administration, similarly to nifedipine, this effect decreased with time and bradycardia was maintained for 24 hours. The hypotensive effect of (-) - mirtenol was explained, in part, by the substance's ability to trigger vasorelaxation in the mesenteric artery. In SHR and NWR animals, (-)- myrtenol (10-6

- 3x10-3 mol/L) triggered concentration-dependent vasodilator activity in the pre-contraction induced by phenylephrine with greater effect in SHR animals (p<0.05). The maximum vasorelaxant effect of the substance occurred independently of the vascular endothelium and involved: (I) blocking the influx of calcium into smooth muscle via L-type voltage-sensitive Ca2 + channels, (II) intracellular Ca2 + mobilization and (III) the decrease in the sensitivity of the contractile machinery to the ion. At lower concentrations, the substance stimulated endothelium-dependent vasorelaxation via nitric oxide in SHR (p <0.05). Together, the results showed beneficial cardiovascular effects of (-) - mirtenol in hypertensive and normotensive animals, making it a promising alternative for the development of a future drug.