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Eur J Pharmacol. 2011 Jan 10;650(1):317-23. doi: 10.1016/j.ejphar.2010.10.032. Epub 2010 Oct 21.

Upregulation of cardiac NOS due to endotoxemia and vagal overactivity contributes to the hypotensive effect of chronic ethanol in female rats.

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1
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina, USA. mahelm@hotmail.com

Abstract

We previously reported that chronic ethanol lowers blood pressure in female rats. In this study, hemodynamic, biochemical, and immunoblot analyses were performed to investigate: (i) the roles of cardiac contractility and autonomic activity in the hypotensive action of ethanol, and (ii) whether endotoxemia-induced upregulation of cardiac and/or vascular nitric oxide synthase (NOS) isoforms underlies the hypotensive and cardiac effects of ethanol. Telemetric monitoring of blood pressure, heart rate, and myocardial contractility (dP/dt(max)) was performed in female rats receiving liquid diet with or without ethanol (5% w/v, 13weeks). Autonomic control was assessed by frequency domain analysis of interbeat intervals (IBI) and systolic blood pressure (SBP). Compared with pair-fed controls, ethanol caused sustained reductions in blood pressure, heart rate, and+dP/dt(max). Ethanol feeding increased the spectral power of high-frequency band (IBI(HF), 0.75-3Hz) and decreased the low-frequency band (IBI(LF), 0.25-0.75Hz) and IBI(LF/HF) ratio, suggesting increased cardiac parasympathetic dominance. In contrast, vascular tone was not affected by ethanol because SBP spectral bands and plasma norepinephrine remained unchanged. Myocardial expressions of eNOS and its upstream regulators, phosphatidylinositol 3-kinase (PI3K) and Akt, and plasma endotoxin and nitrite/nitrate were increased by ethanol. Myocardial iNOS was also increased by ethanol whereas nNOS remained unchanged and aortic levels of all NOS isoforms were not altered by ethanol. These findings suggest that facilitation of myocardial PI3K/Akt/eNOS and iNOS pathways, due possibly to ethanol-induced endotoxemia and/or increased cardiac parasympathetic dominance, might constitute a cellular mechanism for the reduced myocardial contractility and hypotension caused by ethanol in female rats.

PMID:
20970417
PMCID:
PMC3026607
DOI:
10.1016/j.ejphar.2010.10.032
[Indexed for MEDLINE]
Free PMC Article
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