# Mechanisms of hypertension in women with polycystic ovary syndrome

> **NIH NIH R01** · JOHN B. PIERCE LABORATORY, INC. · 2020 · $12,960

## Abstract

ABSTRACT (Parent Grant)
Polycystic ovary syndrome (PCOS) is the most common reproductive endocrinopathy, affecting 1 in 10
reproductive age women. Approximately 75% of women with PCOS have the more severe reproductive and
metabolic PCOS phenotype, which is dominated by features of hyperandrogenism, which include insulin
resistance (IR), compensatory hyperinsulinemia, obesity, subcutaneous and visceral adiposity, dyslipidemia, as
well as increased systolic and diastolic blood pressure and metabolic syndrome. In obese women with androgen
excess (AE)-PCOS, peripheral vascular sympathetic nerve activity is increased. Importantly, free plasma
testosterone level is a predictor of sympathetic nervous system (SNS)-mediated increases in blood pressure and
renin angiotensin system (RAS) activation in women with AE-PCOS. With this application we propose novel
Aims to discover the mechanisms for the androgen effects on the sympathetic contribution to blood pressure
control in women with AE-PCOS and in our novel hyperandrogenemic female (HAF) rat model.
Our overall hypothesis is that androgen excess in women with AE-PCOS leads to increased sympathetic
activation that causes α-adrenergic vasoconstriction and renal sympathetic nervous system activation to
increase blood pressure. Androgen excess also increases angiotensinogen synthesis that would, in turn,
stimulate RAS activity also increasing blood pressure. We will test these hypotheses in women with AE-PCOS
and in a translational manner evaluate mechanisms in our HAF rat model. Aim 1 tests the hypothesis that the
androgenic milieu is the primary driver for sympathetic activation associated with α-adrenergic vasoconstriction,
baroreflex sensitivity and increased blood pressure in AE-PCOS and in the HAF rats. Aim 2 tests the hypothesis
that this androgen-driven sympathetic activation increases RAS activity and BP in AE-PCOS and the HAF rat. A
most exciting, significant and novel aspect of this proposal is the compelling preliminary data demonstrating that
increases in blood pressure are attenuated by α1, β1,2-adrenoceptor blockade and by renal denervation, which is
consistent with our data showing testosterone suppression decreases blood pressure, and suppresses the RAS
and the SNSA in women with AE-PCOS. With its focus on the integration of neural and renal control mechanisms
of blood pressure in AE-PCOS, and its translational studies, concomitant with molecular investigations, this
proposal is a departure from standard investigations of blood pressure regulation. Most importantly, should we
demonstrate a relationship between androgens, SNSA and RAS, modulation of sympathetic activity could be a
valuable treatment to inhibit the underlying causes of AE-PCOS.

## Key facts

- **NIH application ID:** 10088719
- **Project number:** 3R01HL135089-03S1
- **Recipient organization:** JOHN B. PIERCE LABORATORY, INC.
- **Principal Investigator:** Jane F Reckelhoff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $12,960
- **Award type:** 3
- **Project period:** 2018-01-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088719

## Citation

> US National Institutes of Health, RePORTER application 10088719, Mechanisms of hypertension in women with polycystic ovary syndrome (3R01HL135089-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10088719. Licensed CC0.

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