Related Experiment Videos
Tetrahydrobiopterin, a cofactor for NOS, improves endothelial dysfunction during chronic alcohol consumption
1Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, Nebraska 68198-4575, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|October 23, 2001
Summary
Chronic alcohol consumption impairs nitric oxide synthase (NOS)-dependent vasodilation in cerebral arterioles. Supplementation with tetrahydrobiopterin (BH4) improved this impairment, suggesting a BH4 deficiency, not altered eNOS protein, is the cause.
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Pharmacology
Background:
- Alcohol consumption is known to impair vascular function.
- Nitric oxide synthase (NOS) plays a critical role in regulating blood vessel tone, particularly in the brain.
- Impaired NOS-dependent vasodilation in cerebral arterioles is a potential consequence of chronic alcohol intake.
Purpose of the Study:
- To investigate the mechanisms behind impaired nitric oxide synthase (NOS)-dependent vasodilation of cerebral arterioles during alcohol consumption.
- To examine the effect of tetrahydrobiopterin (BH4), a cofactor for NOS, on pial arteriole reactivity in alcohol-fed rats.
- To assess endothelial NOS (eNOS) protein levels in the cerebral vasculature of alcohol-fed and non-alcohol-fed rats.
Main Methods:
- Sprague-Dawley rats were fed liquid diets with or without alcohol for 2-3 months.
- In vivo pial arteriole diameter was measured in response to NOS-dependent (ACh, ADP) and NOS-independent (nitroglycerin) agonists.
- Tetrahydrobiopterin (BH4) was applied exogenously, and its effect on vasodilation was assessed.
- Western blot analysis was used to quantify eNOS protein levels in cerebral microvessels, basilar artery, and aorta.
Main Results:
- Alcohol-fed rats exhibited impaired vasodilation to ACh and ADP compared to non-alcohol-fed rats.
- Vasodilation to nitroglycerin was similar in both groups, indicating preserved smooth muscle function.
- Exogenous BH4 administration improved the impaired vasodilation in alcohol-fed rats but did not affect vasodilation in non-alcohol-fed rats.
- eNOS protein levels were not significantly different between alcohol-fed and non-alcohol-fed rats.
Conclusions:
- Impaired NOS-dependent vasodilation during chronic alcohol consumption is not due to reduced eNOS protein levels.
- The findings suggest that a deficiency in or altered utilization of the NOS cofactor tetrahydrobiopterin (BH4) contributes to alcohol-induced impairment of cerebral vasodilation.
- BH4 supplementation may represent a potential therapeutic strategy to restore cerebral vascular function in the context of alcohol consumption.