Chronic ethanol ingestion induces aortic inflammation/oxidative endothelial injury and hypertension in rats

Abstract

<jats:p> The study aim was to investigate the relationship of chronic ethanol-induced inflammation leading to vascular endothelial injury and elevation of blood pressure (BP) in a rat model. Male Fisher rats were divided into two groups of six animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks and (2) 20% ethanol (4 g kg<jats:sup>-1</jats:sup>, orally) daily for 12 weeks. The mean arterial blood pressure was recorded every week. The animals were anesthetized with pentobarbital after 12 weeks; thoracic aorta were isolated and analyzed for aortic reactivity response, inflammatory mediators, oxidant/antioxidant enzyme protein expression and endothelial nitric oxide-generating system. The results show that the mean BP was significantly elevated 12 weeks after ethanol ingestion. The increased BP was related to increased aortic inflammation (tumor necrosis factor [TNF]-α; nitric oxide synthase [iNOS], COX-2 and MCP-1 protein expression) and elevated angiotensin II levels in alcohol-treated group compared to control. Aortic Nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity, membrane and cytosolic subunits p22<jats:sup> phox</jats:sup> and p47<jats:sup> phox</jats:sup> expression and Mn-SOD activity and protein expression significantly increased, whereas nitric oxide (NO), endothelial NO synthase (eNOS), vascular endothelial growth factor (VEGF)-A and CuZn-SOD activity and protein expression significantly decreased in alcohol-treated group compared to control. The acetylcholine-mediated vasorelaxation response was depressed in the aorta of ethanol-treated rats compared to control. In conclusion, chronic ethanol-induced elevation in BP is related to increased aortic inflammation, elevated angiotensin II levels, induction of NADPH oxidase causing endothelial injury, depletion of CuZn-SOD, down-regulation of endothelial NO generating system and impaired vascular relaxation in rats. </jats:p>

Role of Angiotensin Peptides Precursor in Ethanol Mediated Hepato toxicity: Perspective on Angiotensinogen

“…Thus it is becoming evident that ethanol exposure and increased ROS activate AGT transcription. In an animal model, it ha been shown that the level of Ang II is increased which corresponds to oxidative stress in endothelial cells in rats exposed to ethanol [92,93]. Utilizing the cell based model, our lab has demonstrated increased AGT secretion from human hepatocytes [94,95].The critical question of AGT activation is how these events regulate the hAGT gene during ethanol toxicity.…”

Alcoholism, Fibroblast Growth Factor 23 and Cardiovascular Risk

“…There are many studies relative to the effect of ethanol on nitric oxide synthase, some with contradictory results [56,57] . Raised endothelin-1 levels have been reported in alcoholics [58], but some authors only fi nd these results in advanced (Child C) cirrhotics [59].…”

Estudo da participação da angiotensina II nas disfunções cardiovasculares induzidas pelo consumo crônico de etanol

“…Diversos estudos clínicos e experimentais já demonstraram a associação entre o consumo crônico de etanol e o aumento da pressão arterial, sem que houvesse alteração da freqüência cardíaca (CLARCK, 1985;ABDEL-RAHMAN;WOOLES, 1987). Corroborando com os trabalhos anteriormente descritos (CHAN et al, 1985;HUSAIN et al, 2004HUSAIN et al, , 2005RESTEL et al, 2006RESTEL et al, , 2008FRITZ;RINALDI, 2008;HUSAIN et al, 2011;SHIRPOOR et al, 2012), o modelo de consumo crônico de etanol do presente estudo foi capaz de induzir aumento das pressões arteriais sistólica, diastólica e média, sem apresentar alteração da freqüência cardíaca.…”

“…Estudos avaliando o consumo crônico de etanol em modelos animais demonstraram um aumento plasmático de ANG II, da atividade da ECA e de ANG II (HUSAIN et al, 2011;TAN et al, 2012;YANG et al, 2012 (LARAGH, et al, 1960;MUSABAYANE et al, 1993MUSABAYANE et al, , 1994 RICHMAN, 1982;NIEMINEN et al, 1981;COLLINS et al, 1992). Entretanto, o estudo de Nieminen et al (1985) também não constatou um aumento plasmático de aldosterona, justificado pela redução plasmática de potássio e consequente redução na relação de sódio e potássio.…”

“…Perfis de resposta semelhantes também foram observados no modelo de HAS induzida pelo consumo crônico de etanol (HUSAIN et al, 2011). Tal mecanismo pode estar ocorrendo em nosso modelo de estudo, visto que se observou um aumento significativo da expressão gênica e protéica da COX2 no grupo etanol e sendo esta resposta prevenida pelo tratamento com losartan.…”