Gender‐specific vascular effects elicited by chronic ethanol consumption in rats: a role for inducible nitric oxide synthase

• Published in: British journal of pharmacology 2008-02, Vol.153 (3), p.468-479
• Main Authors: Tirapelli, C R, Fukada, S Y, Yogi, A, Chignalia, A Z, Tostes, R C, Bonaventura, D, Lanchote, V L, Cunha, F Q, Oliveira, A M
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Alcoholism; Alcoholism and acute alcohol poisoning; Animals; aorta; Aorta, Thoracic - metabolism; Biological and medical sciences; Central Nervous System Depressants - pharmacology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Ethanol - pharmacology; ethanol consumption; Female; gender; In Vitro Techniques; inducible nitric oxide synthase; Male; Medical sciences; nitric oxide; Nitric Oxide Synthase Type II - drug effects; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III - drug effects; Nitric Oxide Synthase Type III - metabolism; Ovariectomy; Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Wistar; Research Papers; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Sex Factors; Toxicology; Up-Regulation - drug effects; Vasoconstriction - drug effects; Vasodilation - drug effects
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0707589

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. British Journal of Pharmacology (2008) 153, 468–479; doi:10.1038/sj.bjp.0707589; published online 26 November 2007