Vasorelaxant Effect of 6β-Hydroxybetulinic Acid

Cardiovascular diseases are a major cause of morbidity and mortality worldwide, necessitating the development of novel therapeutic molecules and strategies. A triterpene isolated from the leaves of Licania cruegeriana Urb., Chrysobalanaceae, 6-hydroxybetulinic acid exerts hypotensive effects in hypertensive rats. In this study, we aimed to investigate the vasorelaxant effects of this triterpene in rat aortic rings and determine its possible mechanism of action. The activity of 6-hydroxybetulinic acid was evaluated on contractile responses of isolated aorta to KCl and phenylephrine. 6-Hydroxybetulinic acid induced a concentration-dependent relaxation both in endothelium-intact and endothelium-denuded aortic rings precontracted by phenylephrine (1 µM) and KCl (50 µM). Pretreatment of the aortic rings with N-nitro-l-arginine methyl ester (100 µM), methylene blue (100 µM), or 4-aminopyridine (1 mM), completely prevented 6-hydroxybetulinic acid-induced vasorelaxation, while indomethacin (10 µM) did not affect response. We found that 6-hydroxybetulinic acid exerted its vasorelaxant effects in rat aortic rings in vascular endothelium-dependent and -independent manners by blocking extracellular Ca²⁺ influx. Moreover, its effects were mediated by the activation of the nitric oxide/cyclic GMP pathway and opening of 4-aminopyridine-sensitive K⁺ channels. As vascular tone is a determinant of blood pressure in mammals, our findings partially explain the hypotensive effects of 6-hydroxybetulinic acid in vivo.