# Mechanisms for impaired short-term control of blood pressure with obesity

> **NIH NIH R01** · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2020 · $365,000

## Abstract

Project Summary
Ann M. Schreihofer
Obesity impairs short-term regulation of mean arterial pressure (MAP) by autonomic reflexes, contributing to
the destabilization of MAP. Independent of hypertension, increased variability of MAP is a major risk factor for
end organ damage and stroke. Treatments that ameliorate hypertension but not elevated variability of MAP
leave patients at risk for adverse cardiovascular outcomes. This project uses obese Zucker rats (OZR) to
determine cellular and systemic mechanisms that produce altered autonomic reflexes in the setting of
metabolic syndrome. Like obese humans, adult OZR become hyperinsulinemic with poor glycemic control.
They also develop sympathetically-driven hypertension with diminished baroreflex control of sympathetic nerve
activity (SNA) and heart rate (HR) compared to lean Zucker rats. Other sympatho-inhibitory reflexes processed
through the nucleus tractus solitarius (NTS) are also impaired in adult OZR, coincident with the development of
reduced physiological responses to glutamatergic activation of the NTS. In contrast, glutamatergic activation of
the rostral ventrolateral medulla (RVLM) produces enhanced physiological responses coincident with the onset
of augmented sympatho-excitatory reflexes. This latter condition occurs independent of impaired baroreflexes
and also increases MAP variability. Amelioration of hypertension or impaired glycemic control in adult male
OZR each partially restores baroreflex control of HR, although the fates of NTS function and other sympatho-
inhibitory reflexes are not known. Furthermore, whether these treatments also dampen augmented RVLM
activation and sympatho-excitatory reflexes is unknown. Female OZR develop metabolic syndrome, but
impaired baroreflexes emerge later, well beyond the development of hypertension. The efficacy of treatments
used in males and the functions of NTS, RVLM, and other sympathetic reflexes are unknown in female OZR.
Central hypotheses: In male OZR, poor glycemic control dampens glutamatergic activation of NTS neurons
receiving vagal inputs to impair sympatho-inhibitory reflexes, and this state is exacerbated by hypertension.
Further, we hypothesize that simultaneous ingestion of excess salt with hyperphagia augments glutamatergic
activation of the RVLM to yield exaggerated sympatho-excitatory reflexes that could further destabilize MAP.
Although female rats may develop salt-induced sensitization of the RVLM, we hypothesize estrogen enhances
NTS function to combat impairment of sympatho-inhibitory reflexes in early stages of metabolic syndrome.
We propose to determine how obesity impacts responses of individually recorded NTS and RVLM neurons to
inputs from the periphery and forebrain in male and female OZR compared to age-matched LZR. We will also
determine whether reducing salt intake, poor glycemic control, or MAP alters NTS and RVLM function
coincident with restoration of sympathetic reflexes in OZR. This project will provide novel i...

## Key facts

- **NIH application ID:** 9991893
- **Project number:** 5R01HL132568-04
- **Recipient organization:** UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
- **Principal Investigator:** ANN M SCHREIHOFER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $365,000
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991893

## Citation

> US National Institutes of Health, RePORTER application 9991893, Mechanisms for impaired short-term control of blood pressure with obesity (5R01HL132568-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9991893. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*