Efeitos do carvacrol no sistema renina angiotensina de ratos espontaneamente hipertensos

Abstract

Systemic arterial hypertension (SAH) is a relevant cardiovascular disease for public health, whose hemodynamic changes can cause irreversible damage to target organs, such as the heart and kidneys. In this way, it is salutary to investigate therapies that may contribute to the treatment of SAH, together with the drugs already used in the clinical management of the patient. Carvacrol, a monoterpene presents in essential oils, derived from oregano and thyme, has been evaluated in several experimental protocols to evaluate its effect on the cardiovascular system. The scientific literature reports the vascular effect of carvacrol, with an inhibitory action on calcium channels. More recently, it was demonstrated by our research group, in an innovative way, that this monoterpene, orally, can modulate the gene expression of AT1 and MAS receptors in renal tissue of spontaneously hypertensive rats (SHR), initially suggesting an antihypertensive mechanism that modulates the Renin-Angiotensin System (RAS). However, it was not possible to assess whether carvacrol acts in a dose-dependent or independent manner, its effect on angiotensin I converting enzyme (ACE), or whether it acts on the gene expression of MAS receptors in cardiac tissue. In this context, what we sought in the present consisted of continuing the study of the effect of oral treatment with carvacrol on the modulation of the RAS in SHR, evaluating the serum levels of ACE, Angiotensin 1-7 (Ang 1-7), renal and hepatic hemodynamic and biochemical patterns, lipidogram, in addition to the expression of AT1 and MAS receptors in cardiomyocytes. Twenty-five animals, male, 90 days old, were provided by the Federal University of Maranhão, ensuring normal microclimate conditions, with light-dark cycle (12h:12h), water and standard diet ad libitum. The animals, after adaptation, were randomized into groups: Wistar: normotensive control group treated with sorbitol (Wistar); sorbitol-treated hypertensive control group (SHR-Sorbitol); hypertensive group treated with 50mg of losartan (SHR-Los-50mg); hypertensive group treated with 20mg/kg/day of carvacrol (SHR-Carv-20mg) and hypertensive group treated with 40mg/kg/day of carvacrol (SHR-Carv 40mg). At the end of 30 days, the animals were euthanized for collection of blood and cardiac tissue. Throughout the treatment, the animals had their weight gain and feed intake measured, in addition to their hemodynamic patterns (blood pressure and heart rate) measured by the indirect method, using a plethysmograph, always prior to the gavages. The results show an antihypertensive effect, associated with the regulation of lipid levels. Furthermore, the data indicate an inhibition in the synthesis of ACE I and regulation of the production of Angiotensin 1-7, culminating in the reduction of blood pressure in the groups treated with carvacrol, at normotension levels, for both doses. In continuity, carvacrol promoted downregulation in the expression of AT1 and MAS receptors in cardiac tissue, in a dose-dependent manner. The results suggest that carvacrol is a phytochemical with antihypertensive properties, whose mechanism of action seems to involve, in addition to calcium channels, RAS modulation, more specifically, increase in serum ACEI and expression of cardiac MAS receptors.