title: Endothelial AT₁ and AT₂ pathways in aortic responses to angiotensin II after stress and ethanol consumption in rats.
abstract: Stress and ethanol are important cardiovascular risk factors. Their vascular and blood pressure (BP) effects were evaluated alone and in combination. Adult male Wistar rats (8-10 per group) were separated into control, ethanol (ethanol 20% in drinking water for 6 weeks), stress (restraint 1 h/d 5 d/week for 6 weeks), and ethanol/stress (in combination) groups. Systolic BP was evaluated weekly. Concentration-response curves for contractile responses to angiotensin II in the absence and the presence of losartan (AT1-blocker), PD123-319 (AT2-blocker), L-NAME (nitric oxide synthase inhibitor), or indomethacin (cyclooxygenase inhibitor) were obtained in isolated intact and endothelium-denuded aortas. Effective concentration 50% (EC50) and maximum response (MR) were compared among groups using MANOVA/Tukey tests. Stress and stress plus ethanol increased BP. Ethanol and stress, alone and in combination, did not alter angiotensin responses of intact aortas. PD123-319 decreased MR to angiotensin II in intact aortas from the ethanol and ethanol/stress groups relative to control in the presence of PD123-319. Losartan increased MR to angiotensin II in intact aortas from the stress and ethanol/stress groups relative to control in the presence of losartan. None of the protocols altered angiotensin responses of denuded aortas. Neither indomethacin nor L-NAME altered angiotensin responses of intact aortas from the experimental groups. Thus ethanol and ethanol plus stress may alter endothelial signaling via AT1-receptors, without changing systemic BP. Stress and stress plus ethanol may alter endothelial signaling via AT2-receptors, and thereby increase BP. Knowledge of such vascular changes induced by stress and/or ethanol may contribute to understanding adverse cardiovascular effects of stress and ethanol consumption in humans.
authors.affiliation: Department of Pharmacology, Institute of Biosciences, UNESP - Univ Estadual Paulista , Botucatu, SP , Brazil .
authors.forename: Rafaela de Fátima Ferreira
authors.initials: Rde F
authors.lastname: Baptista
authors.forename: Agnaldo Bruno
authors.initials: AB
authors.lastname: Chies
authors.forename: Elane de Fátima
authors.initials: Ede F
authors.lastname: Taipeiro
authors.forename: Sandra
authors.initials: S
authors.lastname: Cordellini
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects* / Q000378:metabolism / Q000503:physiopathology; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists* / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists* / Q000378:metabolism; D012149:Restraint, Physical; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000975:Antioxidants; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000431:Ethanol; D003345:Corticosterone
keywords: AT1 and AT2 pathways; Angiotensin II; ethanol consumption; nitric oxide; restraint stress; vascular reactivity