# Role of gut commensal Coprococcus comes in angiotensin-converting enzyme inhibitor resistant hypertension

> **NIH NIH R21** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 2022 · $231,750

## Abstract

Project summary and abstract
In the United States, hypertension is a serious public health concern. Resistant hypertension is defined as
hypertension with poor responses to the treatment of at least three classes of antihypertensive drugs, one of
which is diuretic. Despite the availability of multiple classes of antihypertensive drugs, approximately 20% of
hypertensive patients belong to resistant hypertension. Gut microbiota is an emergent and important participant
in the initiation and progression of hypertension. Recently, the gut microbiota is shown to be involved in drug
metabolism and thereafter impacts their efficacies. In vitro and in vivo, our lab has discovered that the gut
commensal Coprococcus comes is capable of catabolizing the angiotensin-converting enzyme (ACE) inhibitor
quinapril. Based on clinical phenotypes of resistant hypertension and our preliminary data, we propose to
investigate the functions of C. comes in the metabolism of ACE inhibitors as well as in the development of
hypertension. The central hypothesis is that C. comes leads to ACE inhibitor resistant hypertension via two
independent mechanisms: (1) it can catabolize ACE inhibitors and reduce their blood pressure-lowering effects;
and (2) it can raise host blood pressure. The specific aims of this study are to investigate the two independent
mechanisms: (1) determine if C. comes can catabolize ACE inhibitors; and (2) determine if C. comes can
increase host blood pressure. To execute these aims, we will conduct in vitro experiments to quantify the
catabolism of the most widely prescribed ACE inhibiors. The blood pressure-lowering effect of ACE inhibitors
will be studied in vivo utilizing hypertensive rat models, whether or not C. comes is present. Experiments on
normotensive and hypertensive rats treated with or without C. comes will be conducted to illustrate the
involvement of C. comes in blood pressure regulation. The long-term objective of this project is to uncover a
novel mechanism by which C. comes contributes to resistant hypertension. Therefore, specific gut microbiota or
gut commensal C. comes alterations would benefit the hypertensive population, particularly resistant
hypertensive patients. The mechanisms behind resistant hypertension remains unclear. Thus, the common
approach to blood pressure control in resistant hypertension is simply the futile addition or substitution of
medications. Given these facts, this project is of great scientific and clinical relevances, since the demonstrating
the mechanistic role of gut commensal C. comes in the etiology of resistant hypertension will lead to potential
strategies for resistant hypertension management and therapy. The National Heart, Lung, and Blood Institute
has announced several reports from working groups to emphasize the research on gut microbiota, sex
differences, and translational barriers. The current proposal is in accordance with these reports and the mission
of the National Institute of Health.

## Key facts

- **NIH application ID:** 10509954
- **Project number:** 1R21AG079357-01
- **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
- **Principal Investigator:** Tao Yang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $231,750
- **Award type:** 1
- **Project period:** 2022-08-04 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10509954

## Citation

> US National Institutes of Health, RePORTER application 10509954, Role of gut commensal Coprococcus comes in angiotensin-converting enzyme inhibitor resistant hypertension (1R21AG079357-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10509954. Licensed CC0.

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