Avaliação do efeito hipotensor e cardiotóxico do extrato aquoso liofilizado das folhas de Annona crassiflora Mart.

Abstract

Hypertension is one of the main causes of morbidity and mortality in the world and is currently the most important risk factor for the development of cardiovascular diseases. A considerable part of the brazilian population uses medicinal plants for the treatment of several diseases, like hypertension. Plant species such as Annona muricata Linn (Annonnaceae), which is used by some communities to control blood pressure, have been the subject of studies that confirmed their hypotensive properties. The species Annona crassiflora Mart. (Annonnaceae), popularly known as araticum, is also used by folk medicine for the treatment of wounds, venereal diseases, cancer, among others. Despite its extensive use in folk medicine, there is no information available reporting that A. crassiflora has a possible effect on the cardiovascular system. Considering that plants of the same genus may present similar phytochemical profiles and consequently, similar physiological activities, the aim of the present study was to evaluate the effect of the lyophilized aqueous extract of A. crassiflora leaves on blood pressure and heart rate of normotensive Wistar rats, as well as to determine the possible mechanisms involved in these effects through the administration of specific antagonists and inhibitors (methylatropin for the evaluation of muscarinic receptors; hexamethonium for the evaluation of autonomic efflux; indomethacin for the evaluation of prostaglandins; L-NAME to evaluate the synthesis and/or release of nitric oxide (NO), glibenclamide to evaluate K+ ATP-dependent channels, nifedipine to evaluate voltage-gated Ca2+ channels). The administration of the extract evoked a significant dose-dependent hypotensive effect, which seems to be mainly related to vasodilatory mechanisms. It has also been observed that the extract has a high dose cardiotoxicity. Investigation of mechanisms related to observed effects revealed that the vasodilation activity of the extract does not seem to involve muscarinic receptor activity, synthesis and/or NO release and peripheral autonomic efflux; that the extract seems to stimulate vasoconstricting and vasodilatory substances that dependent on the activity of cyclooxygenases; that the administration of glibenclamide potentiates the cardiotoxicity induced by the extract; that the blockade of voltage-gated Ca2+ channels is partially responsible for the vasodilator effect of the extract.