# Mechanism of blood pressure lowering by fatty acid nutraceuticals

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $563,500

## 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 
biophysical, biochemical, and whole-­‐‑animal 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 whole-­‐‑animal 
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 of whole animals 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:** 9918934
- **Project number:** 5R01GM121375-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** TOSHINORI HOSHI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $563,500
- **Award type:** 5
- **Project period:** 2017-06-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918934

## Citation

> US National Institutes of Health, RePORTER application 9918934, Mechanism of blood pressure lowering by fatty acid nutraceuticals (5R01GM121375-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9918934. Licensed CC0.

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