# Mineralocorticoid receptor, coronary microvascular function, and cardiac efficiency in hypertension

> **NIH HL R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2026 · $759,113

## Abstract

ABSTRACT
Hypertension is a major risk factor for cardiovascular (CV) morbidity and mortality. Increased CV risk remains
even if blood pressure (BP) is controlled, suggesting there are additional factors associated with hypertension
(influenced by, but independent of, BP per se), which contribute to adverse CV outcomes. This application
focuses on two potentially interrelated CV pathophysiologic processes: 1) impairment in myocardial oxygen
delivery (manifested as coronary microvascular dysfunction, a known predictor of CV morbidity/mortality) and 2)
impairment in cardiac efficiency (manifested as inefficient coupling of myocardial oxygen consumption and
cardiac work). There are no established treatments for coronary microvascular dysfunction or abnormal
cardiac efficiency—a critical knowledge gap. Individuals with hypertension and left ventricular hypertrophy
(LVH) have coronary microvascular dysfunction and excess mineralocorticoid receptor activity. Our overall
hypothesis is that, in individuals with hypertension and LVH, mineralocorticoid receptor blockade will improve
coronary microvascular function and cardiac efficiency, independent of changes in BP; and these improvements
will lead to improved myocardial structure and function and ultimately to improved CV outcomes.
We propose a randomized, controlled, basic experimental study involving humans. Men and women with
hypertension and LVH on enalapril (angiotensin-converting enzyme (ACE) inhibitor) will be randomized to
treatment for 9 months with eplerenone (mineralocorticoid receptor antagonist) or chlorthalidone (thiazide-like
diuretic) + potassium. We will use cardiac PET/CT to quantify changes in coronary microvascular function (i.e.
myocardial flow reserve - ratio of stress/rest myocardial blood flow) and cardiac efficiency (i.e. myocardial
external efficiency - ratio of myocardial work to oxygen consumption); echocardiography to assess changes in
myocardial structure and function; and 24-hr BP monitoring.
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## Key facts

- **NIH application ID:** 11249637
- **Project number:** 5R01HL162960-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Gail Kurr Adler; Marcelo F DI CARLI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $759,113
- **Award type:** 5
- **Project period:** 2023-01-01T00:00:00 → 2026-12-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11249637

## Citation

> US National Institutes of Health, RePORTER application 11249637, Mineralocorticoid receptor, coronary microvascular function, and cardiac efficiency in hypertension (5R01HL162960-04). Retrieved via AI Analytics 2026-06-30 from https://api.ai-analytics.org/grant/nih/11249637. Licensed CC0.

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