Open AccessEthanol consumption increases blood pressure and alters the responsiveness of the mesenteric vasculature in rats
Author(s) -
Tirapelli Carlos R.,
Leone Andreia F. C.,
Yogi Alvaro,
Tostes Rita C.,
Lanchote Vera L.,
Uyemura Sergio A.,
Resstel Leonardo B. M.,
Corrêa Fernando M. A.,
Padovan Cláudia M.,
Oliveira Ana M.,
Coelho Eduardo B.
Publication year - 2008
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/jpp.60.3.0008
Subject(s) - phenylephrine , endocrinology , medicine , mesenteric arteries , enos , indometacin , endothelium , vasodilation , ethanol , nitric oxide , blood pressure , perfusion , nitric oxide synthase , chemistry , anesthesia , cyclooxygenase , biochemistry , artery , enzyme , prostaglandin endoperoxide synthase
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 (E max ) in endothelium‐intact mesenteric bed from both control and ethanol‐treated rats. No differences in the E max values for phenylephrine were observed between groups in the presence of indometacin. l ‐NNA, a nitric oxide (NO) synthase (NOS) inhibitor, increased the E max 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.