The objective of the study was to investigate the mechanism of the relaxant activity of the ent-15α-acetoxykaur-16-en-19-oic acid (KA-acetoxy). In rat mesenteric artery rings, KA-acetoxy induced a concentration-dependent relaxation in vessels precontracted with phenylephrine. In the absence of endothelium, the vasorelaxation was significantly shifted to the right without reduction of the maximum effect. Endothelium-dependent relaxation was significantly attenuated by pretreatment with L-NAME, an inhibitor of the NO-synthase (NOS), indomethacin, an inhibitor of the cyclooxygenase, L-NAME + indomethacin, atropine, a nonselective antagonist of the muscarinic receptors, ODQ, selective inhibitor of the guanylyl cyclase enzyme, or hydroxocobalamin, a nitric oxide scavenger. The relaxation was completely reversed in the presence of L-NAME + 1 mM L-arginine or L-arginine, an NO precursor. Diterpene-induced relaxation was not affected by TEA, a nonselective inhibitor of K+ channels. The KA-acetoxy antagonized CaCl2-induced contractions in a concentration-dependent manner and also inhibited an 80 mM KCl-induced contraction. The KA-acetoxy did not interfere with Ca2+ release from intracellular stores. The vasorelaxant induced by KA-acetoxy seems to involve the inhibition of the Ca2+ influx and also, at least in part, by endothelial muscarinic receptors activation, NO and PGI2 release.

Anacardium occidentale is widely used in folk medicine in Brazil, India, and Africa to treat inflammation, diabetes and hypertension. The aim of the study was to assess the hypotensive, vasorelaxant and antihypertensive effects produced by the hexane extract from the leaves of A. occidentale (HEAO) in rats. The animals were anesthetized, and polyethylene catheters were embedded into the lower abdominal aorta and the inferior vena cava for blood pressure measurements and drug administration. The HEAO was injected and the mean arterial pressure and heart rate were measured. The effects of the HEAO on isolated rat mesenteric rings with and without endothelium were investigated. HEAO induced hypotension and bradycardia in normotensive rats. After pretreatment with L-NAME, indomethacin, atropine or hexamethonium, these effects were attenuated. In mesenteric rings, HEAO antagonized the contractile effects induced by phenylephrine or KCl. This effect was inhibited after removal of the vascular endothelium. Oral administration of the HEAO decreased significant mean arterial pressure in spontaneously hypertensive rats. Mass spectrometric analysis of HEAO identified malic acid and quercetin. Our findings demonstrate that HEAO produces hypotension probably due to a reduction in peripheral vascular resistance, mediated by the endothelium, in part, by a decrease in cardiac output. Bradycardia appears to be due to the indirect activation of cardiac muscarinic receptors via activation of the vagus nerve. The HEAO also induces an antihypertensive effect.