# Mechanisms of hypertensive response sensitization and perinatal programming of hypertension

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $571,587

## Abstract

PROJECT SUMMARY
Work from our laboratory discovered that mild physiological and environmental challenges encountered earlier
in adulthood produce sustained sensitization of the hypertensive response to subsequent hypertensinogenic
challenges. Our recent studies indicate that the adult male offspring of dams with angiotensin II-produced
gestational hypertension or eating a high-fat diet during the perinatal period also display sensitization of the
hypertensive response. Accompanying this exacerbation of the hypertensive response is increased expression
of components of the brain renin-angiotensin-aldosterone system, proinflammatory cytokines and activation of
microglia in forebrain structures controlling sympathetic tone and blood pressure. Importantly, we find that
administering a converting enzyme inhibitor to the sensitized offspring for six weeks between weaning and early
adulthood abrogates gestational hypertension-induced sensitization of the hypertensive response. The present
proposal builds on these findings with experiments that will determine: 1) the critical perinatal period when the
hypertensive response can be sensitized by maternal gestational hypertension, 2) if maternal gestational
hypertension alters mother-offspring behaviors to induce hypertensive response sensitization, 3) whether
inhibitors of microglial activation and proinflammatory cytokines and other blockers of the renin-angiotensin-
aldosterone system will reverse the sensitizing effects of maternal gestational hypertension and maternal
perinatal high-fat diet intake, 4) why young females are protected against hypertensive response sensitization,
5) if maternal gestational hypertension or high-fat diet intake induces sensitized responses to identified
hypertension risk factors related to dietary obesity, sodium intake and what factors are responsible of maintaining
a sensitized response. This information will be obtained by using telemetry to measure blood pressure in freely
moving rats and pharmacological methods to test mechanisms mediating hypertensive response sensitization.
In addition molecular expression methods be used to characterize changes in mRNA and protein expression in
key CNS regions controlling blood pressure. Completion of the proposed experiments will result in the delivery
of important new information on how fetal programming results in increasing the likelihood of expression of
enhanced hypertension later in life and measures that can be used to prevent it.

## Key facts

- **NIH application ID:** 10171885
- **Project number:** 5R01HL139575-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** ALAN Kim JOHNSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $571,587
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171885

## Citation

> US National Institutes of Health, RePORTER application 10171885, Mechanisms of hypertensive response sensitization and perinatal programming of hypertension (5R01HL139575-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10171885. Licensed CC0.

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