# Fatty acid and alcohol modulation of cerebral artery diameter

> **NIH NIH R03** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $76,000

## Abstract

Episodic drinking with blood alcohol levels reaching 35-80 mM is associated with an increased risk for
cerebrovascular ischemia, stroke, and death from ischemic stroke. Cerebral ischemia may result from
enhanced constriction of cerebral arteries. In a rat model widely used to mimic human cerebral artery function,
our group previously demonstrated that alcohol-induced cerebrovascular constriction is mediated by vascular
smooth muscle (VSM) Ca2+/voltage-gated K+ channels of large conductance (BK channels). BK channels are
critical regulators of arterial diameter and myogenic tone. VSM BK channel activation results in outward
potassium currents that hyperpolarize the membrane, leading to diminished smooth muscle cell (myocyte)
contractility. Thus, BK current inhibition by alcohol results in cerebral artery constriction. Factors that tune BK
channel sensitivity to alcohol remain largely unknown.
 Our group has established that high-cholesterol diet that leads to elevated blood cholesterol (CLR)
levels and hypercholesterolemia protects against alcohol-induced constriction via accumulation of CLR in
cerebral artery tissue. Clinical trial evidence supports the use of omega-3 fatty acids (FAs) such as
docosahexaenoic acid (DHA) as a dietary supplement to reduce CLR buildup in arterial tissue. Moreover, DHA
represents one of the most prevalent fatty acids in the brain. Whether increase in DHA can modify effect of
alcohol and CLR-alcohol interactions in control of BK channel activity and cerebral artery diameter remains
unknown. To cover existing gap in knowledge we will address two independently testable yet related Specific
Aims: 1) we will determine the impact of DHA on alcohol-induced constriction of cerebral artery at naïve versus
elevated CLR in arteries with intact and removed endothelium; 2) we will determine the BK protein structural
basis of DHA effect on alcohol sensitivity of BK current in cerebral artery smooth muscle.
 In the course of the study, we will capitalize on our strong expertise in lipid modulation of alcohol effect
on cerebral artery smooth muscle. We will utilize rat model of dietary lipid delivery, cerebral artery diameter
monitoring in vivo and in vitro, biochemical determination of DHA and CLR levels, site-directed mutagenesis,
tissue loading with engineered DNA, and BK channel knock-out mouse.
 Our proposal will for the first time establish the role of DHA in the alcohol-driven effect at the organ
level of cerebral artery. Also, for the first time we will unveil molecular mechanism that enables FA-alcohol
interplay in control of cerebral artery diameter. Considering that DHA dietary supplementation in clinical
practice is widely recommended during multiple pathological conditions (such as hypercholesterolemia,
atherosclerosis, Alzheimer’s disease, inflammation, etc.) data obtained during our study will have high
translational value.

## Key facts

- **NIH application ID:** 9952069
- **Project number:** 1R03AA028380-01
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Anna Bukiya
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $76,000
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952069

## Citation

> US National Institutes of Health, RePORTER application 9952069, Fatty acid and alcohol modulation of cerebral artery diameter (1R03AA028380-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952069. Licensed CC0.

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