# Sex Differences in Blood Pressure and Olfactory Receptor 558 (OLFR558)

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $616,008

## Abstract

Project Summary
Premenopausal females have blood pressure that is ~10mmHg lower than that of males. We previously
reported that an evolutionarily conserved olfactory receptor, OLFR558, is expressed in the kidney. We have
now found that sex differences in blood pressure are absent in Olfr558 knockout (KO) mice, primarily due to
increased blood pressure in females, along with a decreased diastolic pressure in males. In Aim 1, we will
determine which OLFR558-expressing cell types are primarily responsible for the blood pressure phenotype in
males and females. OLFR558 is expressed both in the vasculature and in the renal afferent arteriole (where
renin is stored and secreted from); thus, we will examine both renin levels and vascular responses in male and
female whole-animal KO mice. In addition, we will examine these same parameters, along with blood pressure
by telemetry, in mice with tissue-specific Olfr558 rescue only in the vasculature, or, only in renin-expressing
cells. In Aim 2, we will use gonadectomy in wild-type and KO mice to test the hypothesis that OLFR558 relies
on gonadal signals to mediate sex differences. In parallel experiments we will use the four core genotype
model, in which gonadal and chromosomal sex are separately inherited, to further interrogate this hypothesis.
Finally, it is well-established that males have a higher incidence of hypertension than premenopausal females;
this is true both in humans, and, in animal models of hypertension. In Aim 3, we will examine how OLFR558
influences sex differences in hypertension using two different hypertension models (Angiotensin II infusion,
and, DOCA/Salt). In sum, these studies will reveal key insights into the function of an evolutionarily conserved
OR which is required for sex differences in blood pressure.

## Key facts

- **NIH application ID:** 10854565
- **Project number:** 1R01DK139021-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jennifer L Pluznick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $616,008
- **Award type:** 1
- **Project period:** 2024-05-03 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10854565

## Citation

> US National Institutes of Health, RePORTER application 10854565, Sex Differences in Blood Pressure and Olfactory Receptor 558 (OLFR558) (1R01DK139021-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10854565. Licensed CC0.

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