Research Paper
Subject Category: Cardiovascular and pulmonary pharmacology
British Journal of Pharmacology (2008) 153, 468–479; doi:10.1038/sj.bjp.0707589; published online 26 November 2007
Gender-specific vascular effects elicited by chronic ethanol consumption in rats: a role for inducible nitric oxide synthase
C R Tirapelli1, S Y Fukada2, A Yogi3, A Z Chignalia3, R C Tostes3, D Bonaventura4, V L Lanchote5, F Q Cunha2 and A M de Oliveira4
- 1Department of Psychiatry Nursing and Human Sciences, College of Nursing of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil
- 2Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil
- 3Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, São Paulo, Brazil
- 4Department of Physics and Chemistry, Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil
- 5Laboratory of Toxicology, Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil
Correspondence: Dr AM de Oliveira, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, Ribeirão Preto, São Paulo, CEP 14040-903, Brazil. E-mail: amolive@usp.br
Received 16 July 2007; Revised 10 August 2007; Accepted 23 October 2007; Published online 26 November 2007.
Abstract
Background and purpose:
Epidemiological data suggest that the risk of ethanol-associated cardiovascular disease is greater in men than in women. This study investigates the mechanisms underlying gender-specific vascular effects elicited by chronic ethanol consumption in rats.
Experimental approach:
Vascular reactivity experiments using standard muscle bath procedures were performed on isolated thoracic aortae from rats. mRNA and protein for inducible NO synthase (iNOS) and for endothelial NOS (eNOS) was assessed by RT-PCR or western blotting, respectively.
Key results:
In male rats, chronic ethanol consumption enhanced phenylephrine-induced contraction in both endothelium-intact and denuded aortic rings. However, in female rats, chronic ethanol consumption enhanced phenylephrine-induced contraction only in endothelium denuded aortic rings. After pre-incubation of endothelium-intact rings with L-NAME, both male and female ethanol-treated rats showed larger phenylephrine-induced contractions in aortic rings, compared to the control group. Acetylcholine-induced relaxation was not affected by ethanol consumption. The effects of ethanol on responses to phenylephrine were similar in ovariectomized (OVX) and intact (non-OVX) female rats. In the presence of aminoguanidine, but not 7-nitroindazole, the contractions to phenylephrine in rings from ethanol-treated female rats were greater than that found in control tissues in the presence of the inhibitors. mRNA levels for eNOS and iNOS were not altered by ethanol consumption. Ethanol intake reduced eNOS protein levels and increased iNOS protein levels in aorta from female rats.
Conclusions and implications:
Gender differences in the vascular effects elicited by chronic ethanol consumption were not related to ovarian hormones but seemed to involve the upregulation of iNOS.
Keywords:
ethanol consumption, aorta, gender, nitric oxide, inducible nitric oxide synthase
Abbreviations:
eNOS, endothelial nitric oxide synthase; iNOS, inducible nitric oxide synthase; L-NAME, NG-nitro-L-arginine methyl ester; 7-NI, 7-nitroindazole; nNOS, neuronal nitric oxide synthase; NOS, nitric oxide synthase; OVX, ovariectomy; SNP, sodium nitroprusside
