Ethanol consumption increases blood pressure and alters the responsiveness of the mesenteric vasculature in rats

Abstract

Chronic ethanol consumption and hypertension are related. In the current study we investigated whether changes in reactivity of the mesenteric arterial bed could account for the increased blood pressure associated with chronic ethanol intake. Changes in reactivity to phenylephrine and acetylcholine were investigated in the perfused mesenteric bed from rats treated with ethanol for 2 or 6 weeks and their age-matched controls. Mild hypertension was observed in chronically ethanol-treated rats. Treatment of rats for 6 weeks induced an increase in the contractile response of endothelium-intact mesenteric bed to phenylephrine, but not denuded rat mesenteric bed. The phenylephrine-induced increase in perfusion pressure was not altered after 2 weeks' treatment with ethanol. Moreover, acetylcholine-induced endothelium-dependent relaxation was reduced by ethanol treatment for 6 weeks, but not 2 weeks. Pre-treatment with indometacin, a cyclooxygenase inhibitor, reduced the maximum effect induced by phenylephrine (Emax) in endothelium-intact mesenteric bed from both control and ethanol-treated rats. No differences in the Emax values for phenylephrine were observed between groups in the presence of indometacin. L-NNA, a nitric oxide (NO) synthase (NOS) inhibitor, increased the Emax for phenylephrine in endothelium-intact mesenteric bed from control rats but not from ethanol-treated rats. Levels of endothelial NOS (eNOS) mRNA were not altered by chronic ethanol consumption. However, chronic ethanol intake strongly reduced eNOS protein levels in the mesenteric bed. This study shows that chronic ethanol consumption increases blood pressure and alters the reactivity of the mesenteric bed. Moreover, the increased vascular response to phenylephrine observed in the mesenteric bed is maintained by two mechanisms: an increased release of endothelial-derived vasoconstrictor prostanoids and a reduced modulatory action of endothelial NO, which seems to be associated with reduced post-transcriptional expression of eNOS.

Contribution of oxidative stress and prostanoids in endothelial dysfunction induced by chronic fluoxetine treatment

“…For example, increased contractility in response to phenylephrine is described when eNOS is down-regulated in the vasculature [34,35]. Similarly, decreased vascular expression of nNOS is associated with a hyper-reactivity to phenylephrine [36].…”

Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms

“…The concentration of ethanol used in the present investigation was based on previous studies in different types of blood vessels [5,6,14,18]. In the present work, we used concentrations of ethanol higher then those described in the bloodstream of humans (50-200 mmol/l) [19] or rats (20-45 mmol/l) [1,2,20] after ethanol ingestion. This procedure was adopted in order to induce an increase in tension that would allow for the investigation of putative mechanisms underlying contractile actions of ethanol.…”

“…Ethanol intake constitutes an important cardiovascular risk factor in the general population, and increased prevalence of hypertension has been shown in heavy drinkers [33]. Direct contractile responses induced by ethanol as well as a myogenic mechanism involving alteration of contractile properties of VSMC contribute to the enhanced blood pressure associated with ethanol consumption [2,6,18].…”

“…Several studies in animals and humans have demonstrated that ethanol consumption is associated with cardiovascular pathologies such as hypertension [1][2][3]. In fact, ethanol can evoke direct contractile responses in different blood vessels [4][5][6].…”

Consequências do consumo crônico de etanol sobre a reatividade e expressão dos componentes do sistema endotelinérgico em corpo cavernoso de rato

“…Seu uso indevido é um dos principais fatores que contribui para a diminuição da saúde mundial sendo responsável por 3,8% das mortes. (Sun;Mayhan, 2001;Husain et al, 2005Husain et al, , 2007Tirapelli et al, 2008a). O etanol tem sido descrito como um importante indutor de disfunção endotelial que leva a alteração da reatividade vascular em aorta (Tirapelli et al, 2006a), carótida (Tirapelli et al, 2006b), leito mesentérico (Tirapelli et al, 2008a) e circulação peniana (Lizarte et al, 2009).…”