Down-regulation of ventricular nitric oxide generating system in chronic alcohol-treated hypertensive rats

Area of Science:

• Cardiovascular Physiology
• Molecular Cardiology
• Toxicology

Background:

• Epidemiological studies suggest low-to-moderate alcohol intake benefits cardiac health.
• Conversely, chronic high-dose alcohol consumption is linked to cardiovascular complications, including hypertension.
• The precise molecular mechanisms underlying chronic ethanol-induced hypertension remain unclear.

Purpose of the Study:

• To investigate the relationship between chronic ethanol exposure, elevated blood pressure, and cardiac endothelial nitric oxide (NO) levels.
• To explore the impact of ethanol on the nitric oxide generating system within the heart's endothelium.

Main Methods:

• Male Fisher rats were administered ethanol (20%, 4 g/kg daily) or a sucrose control for 12 weeks.
• Systolic, diastolic, and mean blood pressure (BP) were monitored using the tail-cuff method.
• Heart tissue, specifically the left ventricle, was analyzed for nitric oxide, endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF) via ELISA and Western blotting.

Main Results:

• Chronic ethanol ingestion led to a significant increase in systolic, diastolic, and mean BP compared to controls (p<0.001).
• Nitric oxide levels were significantly reduced in the left ventricles of ethanol-treated rats.
• Protein expression of eNOS and gene/protein expression of VEGF were significantly down-regulated in the cardiac endothelium of ethanol-exposed rats.

Conclusions:

• Chronic ethanol consumption induces hypertension in rats.
• This hypertension is associated with endothelial oxidative injury and a down-regulated nitric oxide generating system in the left ventricle.
• The findings elucidate a key mechanism contributing to alcohol-induced cardiovascular damage.