# Mechanism of blood pressure lowering by fatty acid nutraceuticals

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $39,767

## Abstract

Project Summary
Long-chain polyunsaturated omega-3 fatty acids, such as docosahexaenoic acid (DHA) with a 22-carbon
chain, are found abundantly in oily fish including anchovy, herring, mackerel, and salmon. These
omega-3 fatty acids are widely thought to have multiple health-promoting effects. Evidence suggests
that DHA decreases blood pressure, especially in hypertensive patients. We hypothesize that the
hypotensive action of DHA is mediated by its stimulatory effect on large-conductance calcium and
voltage-gated potassium (Slo1 BK) channels important in blood pressure regulation. The research
program proposed here will provide molecular and atomic basis of the hypotensive action of DHA
involving Slo1 BK channels using a variety of methods. We postulate that a hydrogen bond between a
tyrosine residue in the S6 segment of the channel and the carboxylate group is critical in destabilizing the
closed conformation of the ion conduction gate and this interaction underlies the hypertensive action.
Using the physicochemical principles elucidated, we will rationally design, synthesize and test fatty-acid
activators of Slo1 BK channels. The anticipated outcome of the research program has potential to explain
blood pressure regulation based on the hydrogen bonds formed between specific tyrosine residues of the
Slo1 BK channel and DHA and provide a solid mechanistic foundation for discovery and development
of pharmaceuticals and nutraceuticals for blood pressure management.

## Key facts

- **NIH application ID:** 10134062
- **Project number:** 3R01GM121375-04S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** TOSHINORI HOSHI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,767
- **Award type:** 3
- **Project period:** 2017-06-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134062

## Citation

> US National Institutes of Health, RePORTER application 10134062, Mechanism of blood pressure lowering by fatty acid nutraceuticals (3R01GM121375-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10134062. Licensed CC0.

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