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

Award Number: R01DK139021
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/03/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2028
AWARD TERMINATION DATE: 04/30/2025

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $616,008 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/6/2026	NON-COMPETING CONTINUATION	$616,008
														Subtotal = $616,008

Issue Date FY: 2025 ( Subtotal = $616,008 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	4/30/2025	NON-COMPETING CONTINUATION	$616,008
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/29/2025	TERMINATION	$0
														Subtotal = $616,008

Issue Date FY: 2024 ( Subtotal = $664,725 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	8/21/2024	SUPPLEMENT FOR EXPANSION	$48,717
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	5/3/2024	NEW	$616,008
														Subtotal = $664,725

Grand Total All Awards = $1,896,741

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

Award Number: R01DK139021

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/03/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2028

AWARD TERMINATION DATE: 04/30/2025

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