Vasorelaxation induced by the essential oil of Croton nepetaefolius and its constituents in rat aorta are partially mediated by the endothelium

Abstract

Previously, we reported that essential oil of Croton nepetaefolius (EOCN) decreases blood pressure in normotensive rats, an effect that seems resulting from its vasodilatory action directly upon vascular smooth muscle. In the present study, we aimed to study the role of endothelium-nitric oxide pathway in the mediation of vasodilatory effects of EOCN and two of its constituents, methyleugenol and alpha-terpineol, using rat isolated thoracic aorta and mesenteric vascular bed preparations. EOCN (1-300 microg/mL), in a concentration-dependent manner, relaxed isolated endothelium-intact aortic rings precontracted with KCl 60 mM, with an IC(50) value of 26.7 (14.7-48.2) microg/mL. Either pretreatment of the tissue with L-NAME, a nitric oxide synthase inhibitor, or mechanical endothelium removal increased significantly the IC(50) value to 66.6 (52.7-84.1) or 105.6 (91.3-122.2) microg/mL, respectively. In endothelium-intact aortic rings precontracted with norepinephrine, EOCN (10-200 microg/mL) produced a vasorelaxant action which was decreased by the pretreatment of the aortic rings with methylene blue, a guanylate cyclase inhibitor. In mesenteric bed preparations perfused under constant pressure, EOCN reverted the reduction of mesenteric flow caused by KCl (60 mM), an effect that was attenuated by L-NAME. Vasodilator responses to EOCN in mesenteric bed preparations were mimicked by methyleugenol and alpha-terpineol, and were also significantly reduced in the presence of L-NAME. In conclusion, EOCN has vasorelaxant effects in both a resistance vascular bed and in a conduit artery. They seem attributed, at least in part, to the actions of its main constituents methyleugenol and alpha-terpineol and appear partially dependent upon the integrity of a functional vascular endothelium. Inhibition of other transduction pathways may be involved in the mediation of these effects.

Cardiovascular effects of monoterpenes: a review

“…The authors demonstrated that α-terpineol had a hypotensive effect in rats at a dose of 5 mg/kg administered intravenously. Magalhães et al (2008), using perfused rat mesenteric vascular bed, showed that α-terpineol also induces vasorelaxation which was abolished in the presence of L-NAME, suggesting the involvement of NO in this vasorelaxation. Possibly the hypotensive effects reported by Saito et al (1996) may have been caused by a reduction in peripheral vascular resistance as a result of vasorelaxation (Magalhães et al, 2008).…”

“…Besides the activities described above, monoterpenes also produce significant effects on the cardiovascular system, promoting, among other actions, vasorelaxation, decreased heart rate, and hypotension (Peixoto-Neves et al, 2010;Bastos et al, 2010;Aydin et al, 2007;Magalhães et al, 2008). Thus, these monoterpenes can be useful as agents for prevention and/or treatment of cardiovascular diseases (CVD).…”

“…Monoterpenes, as well as the sesquiterpenes In vivo Normotensive rat Hypotension Lahlou et al (2003) In vivo DOCA-salt hypertensive rat Antihypertensive effect Lahlou et al (2003) Terpineol (29) In vivo Rat Hypotension Saito et al (1996) In vitro Rat isolated mesenteric vascular bed Vasorelaxation Magalhães et al (2008) In vivo Conscious rats Hypotension Ribeiro et al (2010) In vitro Rat isolated mesenteric Vasorelaxation Ribeiro et al (2010) and diterpenes, are secondary metabolites because they are classified as nonessential for viability; however, they mediate important interactions between plants and their environment (Chappell, 1995). Several monoterpenes are widely used in the agriculture, cosmetic, and food industries, and as a general antiseptic in medical practice (Aeschbach et al, 1994;Lee et al, 1997;Manou et al, 1998).…”

Análise de terpenóides de espécies de Croton sect. Lamprocroton (Mull. Arg.) Pax (Euphorbiaceae)

“…Em termos industriais, são utilizados em aromatizantes e perfumes (Buchanan et al, 2000). Em termos farmacológicos possuem uma grande gama de propriedades medicinais como antibacteriana (Suarez et al, 2005;Siminionato et al, 2007;, antisséptica, antihelmíntica, anti-inflamatória (Santos et al, 2005), anticâncer (Sylvestre et al, 2006;Compagnone et al, 2010), antinociceptiva (Abdon et al, 2002;Santos et al, 2005), antioxidante (Agnaniet et al, 2005;Morais et al, 2006;Simionatto et al, 2007;Mohamed et al, 2009), carminativa, expectorante, fungicida (Souza et al, 2006), gastoprotetora (Santos et al, 2005), inseticida , larvicida (Lima et al, 2006;Torres et al, 2008) e vasorrelaxante (Magalhães et al, 2008 Alguns monoterpenos são notavelmente diferenciados. Carvacrol, timol e ρ-cimeno são monoterpenos fenólicos.…”

“…Triterpenos e esteróides são compostos bastante comuns em Euphorbiaceae (Martinez-Vasquez et al, 1999;Wansi et al, 2006;Rubalcava et al, 2007) 18-4,4,6a,6b,8a,11,11,14b-Octametil-1,4,5,6,6a,6b,7,8, 9,10,11,12,14,14a, 19 -ácido ursenóico 28 -ergost-5-en-3-ol (Agarwal et al, 2003;Mendes et al, 2004;Magalhães et al, 2008) anti-leischmania (Cardoso-Lopes et al, 2009) e anti-artrite (Magalhães et al, 2008). Em Croton são descritos para um grande número de espécies, como C. zambesicus (Mohamed et al, 2009), C. tiglium (Mendes et al, 2004), C. betulaster (Barbosa et al, 2003), C. eluteria (Fattorusso et al, 2002) e C. pulley (Abreu et al, 2001).…”