Thursday, February 19, 2026 2/19/2026

Contribution of Orexin System to Hypertension

Award Number: R01HL163159
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

Group Awards By:

View Award Description

Contribution of Orexin System to Hypertension - SUMMARY Hypertension is a major risk factor for cardiovascular disease, with salt sensitive hypertension (SSH) accounting for 51% of all cases. As augmented sympathetic nerve activity (SNA) and dysregulated neuroendocrine secretion are known to play critical roles in the development of SSH, w e propose a study to investigate the mechanisms whereby hyperactivity of the brain orexin system, may critically influence SNA and neuroendocrine dysregulation, thus contributing to SSH development. Orexin A (OXA) is a multifunctional neuropeptide produced by hypothalamic neurons that plays various physiological roles, including cardiovascular function, through binding with its receptors. Recent studies show that upregulation of brain orexin signaling occurs in several animal models of hypertension suggesting implications for overactive brain orexin signaling in hypertension development. However, the impact of orexin system in the development of SSH and detailed molecular mechanisms underlying orexin system mediated hypertension development are poorly understood. Our preliminary data shows that a high salt (HS) diet results in hypertension, and significantly increases expression of OXA and orexin 1 receptor (OX1R) in the hypothalamic paraventricular nucleus (PVN) of Dahl salt sensitive (Dahl S) rats, an animal model for human SSH, but not in salt resistant rats. Interestingly, HS diet intake in Dahl S rats also increases OX1R expression in adrenal glands, a component of hypothalamic-pituitary- adrenal (HPA) axis which is a central neuroendocrine response system to combat stress and regulate multiple physiological functions. The PVN controls SNA outflow and neuroendocrine hormone, such as vasopressin (AVP) and corticotropin-releasing hormone (CRH), production. Central administration of OXA increases SNA outflow and PVN AVP expression as well as plasma corticosterone levels, a hallmark of HPA axis activation. Hyperactivity of HPA axis is involved in multiple diseases including hypertension. Lesions in the PVN prevent high salt induced hypertension in Dahl S rats. This body of evidence suggests that PVN OX1R activation is involved in SNA and HPA axis regulation, and increased PVN OXA-OX1R signaling induced by high salt intake may stimulate neuroendocrine systemic secretion, trigger long-term adaptive changes through regulating downstream gene expression, producing excessive excitatory neurochemicals, resulting in augmented PVN sympathetic tone, and leading to SSH. The objectives of this project are: (i) investigate whether chronic knockdown of PVN OX1R expression decreases plasma corticosterone levels, attenuate HS induced increase in SNA, and prevent SSH; (ii) elucidate the molecular mechanism underlying the relationship between OXA-OX1R and its augmentation of SNA and dysregulation of HPA axis. A combination of in vivo gene transduction, electrophysiological recordings, and molecular and biochemical approaches will be employed to answer our questions using salt sensitive and normotensive rat models. Our studies may identify new targets for therapeutic intervention in hypertension.


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 = $0 )
2026	2025	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cardiovascular Diseases Research	000	4	2/9/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $439,240 )
2025	2025	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cardiovascular Diseases Research	001	4	7/14/2025	NON-COMPETING CONTINUATION	$43,924
2025	2025	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cardiovascular Diseases Research	000	4	3/31/2025	NON-COMPETING CONTINUATION	$395,316
														Subtotal = $439,240

Issue Date FY: 2024 ( Subtotal = $430,457 )
2024	2024	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cardiovascular Diseases Research	001	3	6/20/2024	NON-COMPETING CONTINUATION	$35,140
2024	2024	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cardiovascular Diseases Research	000	3	3/25/2024	NON-COMPETING CONTINUATION	$395,317
														Subtotal = $430,457

Issue Date FY: 2023 ( Subtotal = $439,242 )
2023	2023	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cardiovascular Diseases Research	000	2	3/27/2023	NON-COMPETING CONTINUATION	$439,242
														Subtotal = $439,242

Issue Date FY: 2022 ( Subtotal = $348,179 )
2022	2022	MICHIGAN TECHNOLOGICAL UNIVERSITY	1400 TOWNSEND DR	HOUGHTON	MI	49931	HOUGHTON	USA	Cardiovascular Diseases Research	000	1	4/13/2022	NEW	$348,179
														Subtotal = $348,179

Grand Total All Awards = $1,657,118

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Contribution of Orexin System to Hypertension

Award Number: R01HL163159

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer