Hypotensive effect of Aspidosperma subincanum Mart. in rats and its mechanism of vasorelaxation in isolated arteries Milton Junio Cˆ andido Bernardes a , Fla ´ vio Silva de Carvalho a , Ludmila Lima Silveira b , Jose ´ Realino de Paula a , Maria Teresa Freitas Bara a , Cle ´ via Ferreira Garrote a , Gustavo Rodrigues Pedrino b , Matheus Lavorenti Rocha a,n a Faculty of Pharmacy, Federal University of Goias, Avenida Universita ´ria s/n, 74605-220 Goiˆ ania, GO, Brazil b Biological Sciences Institute, Federal University of Goias, Campus Samambaia, Caixa Postal 131, 74001-970 Goiˆ ania, GO, Brazil article info Article history: Received 22 August 2012 Received in revised form 22 October 2012 Accepted 28 October 2012 Available online 14 November 2012 Keywords: Aspidosperma subincanum Vasorelaxation Artery Blood pressure abstract Ethnopharmacological relevance: Aspidosperma subincanum is a medicinal herb that is known to be useful for the treatment of cardiovascular-related illnesses. However, its effects and pharmacological mechanisms of action have not been studied. The aim of the present study was to determine the effect of an ethanol extract of Aspidosperma subincanum (EEAS) on blood pressure (in vivo) and vascular tension (in vitro) in the rat thoracic aorta. Materials and methods: Catheters were inserted into the right femoral vein and artery of anesthetized rats for EEAS infusion and the measurement of blood pressure, heart rate and aortic blood flow (flow probes were placed around the aorta). Moreover, the vasodilator effect of EEAS in isolated pre-contracted rat aortas was examined. Results: Intravenous infusion of EEAS resulted in significant and dose-dependent hypotension, bradycardia and increased aortic blood flow. In isolated arteries, EEAS (0–27 mg/mL) induced a concentration-dependent relaxation of pre-contracted aortic rings; endothelial denudation potentiated this effect. Pre-treatment of the aortic rings with ODQ, an inhibitor of soluble guanylyl cyclase (sGC); MDL-12,330A, an inhibitor of adenylyl cyclase (AC); or CPA, a SERCA inhibitor, reduced EEAS-induced vasorelaxation. Treatment with an EEAS impaired contractions induced by phenylephrine (an adrenergic agonist) and Bay K 8644 (an L-type Ca 2 þ channel activator). The blockade of K þ channels with tetraethylammonium, clotrimazole, glibenclamide or 4-aminopyridine reduced the relaxation stimulated by EEAS. Conclusions: These findings suggest that EEAS induces hypotension associated with bradycardia. EEAS induces endothelium-independent vascular relaxation. The sGC/cGMP and AC/cAMP pathways, SERCA activation and Ca 2 þ and K þ flux across the sarcolemma, are likely involved in this relaxation. & 2012 Published by Elsevier Ireland Ltd. 1. Introduction Hypertension is the main risk factor for heart attack, stroke and coronary and renal vascular disease. These cardiovascular diseases affect millions of people around the world and cause morbidity, mortality and a serious economic burden (Carretero and Oparil, 2000; Gupta et al., 2010). Although hypertension is easily diagnosed and can be managed using pharmacological interventions, some drugs that are available for the treatment of hypertension are ineffective and/or have multiple side effects. However, medicinal plants have a long history of use for the treatment of hypertension; they are known to induce hypotension with minimal side effects (Chan et al., 2000; Greenway et al., 2011). The regulation of the vascular tone is very important to the appropriate control of blood pressure. Contraction and dilation of blood vessels in response to physiological demands are controlled by changes in cytosolic Ca 2 þ levels in vascular smooth muscle cells, which directly control blood pressure. Physiologically, vascular relaxation is induced by an increase in the intracellular concentrations of the cyclic nucleotides 3 0 ,5 0 -cyclic adenosine monophosphate (cAMP) and 3 0 ,5 0 -cyclic guanosine monopho- sphate (cGMP), which leads to a reduction in the concentration of intracellular Ca 2 þ (Lincoln, 1990). cAMP and cGMP can act on various targets to regulate Ca 2 þ mobilization and induce relaxa- tion in vascular smooth muscle. For example, they can stimulate the sarcoplasmic Ca 2 þ -ATPase pumps and thereby increase Ca 2 þ uptake into the stores or stimulate Ca 2 þ efflux from the cells Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/jep Journal of Ethnopharmacology 0378-8741/$ - see front matter & 2012 Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.jep.2012.10.057 n Corresponding author. Tel.: þ55 62 3209 6440; fax: þ55 62 32096037. E-mail address: matheusroch@yahoo.com.br (M.L. Rocha). Journal of Ethnopharmacology 145 (2013) 227–232