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Renal Sensory Nerve Contribution to Hypertension

Award Number: K01HL159047
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/27/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Renal Sensory Nerve Contribution to Hypertension - PROJECT SUMMARY/ABSTRACT: High blood pressure is a leading cause of morbidity and mortality worldwide and greatly contributes to a multitude of cardiovascular disease. Although the renal sympathetic nerves have been the focus of many basic and clinical studies, the role of the renal afferent (sensory) nerves in mediating hypertension remains poorly understood. Activation of renal afferents can potentially either excite or inhibit global sympathetic nerve activity and thereby increase or decrease blood pressure, but the precise mechanisms controlling the balance of the excitatory vs. inhibitory reflex actions of the renal afferent nerves are currently unknown. We have recently determined that the endothelin-1 (ET-1) system significantly modulates renal afferent nerves. Our central hypothesis is that endothelin A (ETA) receptor activation on renal afferent nerves increases sympathetic nerve activity and blood pressure, and that endothelin B (ETB) receptor activation on renal afferent nerves decreases sympathetic nerve activity and blood pressure. We will test this hypothesis using rodent models in the settings of both normal physiology and hypertension. ETA or ETB receptors on renal nerves will be directly activated in rats instrumented with radiotelemetry devices, which allow for recording of blood pressure and markers of sympathetic nerve activity in unrestrained, conscious animals. These experiments, which will also include in vitro culturing, imaging, and electrophysiological examination of renal afferent nerves will provide important new information about the mechanisms of afferent nerve activation. High salt and high fat content are common features of the typical Western diet and are well-known to play a role in the development of many cardiovascular diseases such as hypertension. Our preliminary evidence indicates that these factors also increase renal afferent nerve expression of ET-1 and ETA receptors. Because of this connection to increases in abberant renal afferent nerve activity and blood pressure, we will also test the hypothesis that high salt or high fat diet increases afferent nerve ET-1 expression and a preponderance of ETA to ETB receptor signaling promoting increased afferent nerve activity, sympathetic tone, and blood pressure. This hypothesis will be tested through the use of rat models with specific pharmacological inhibition of ETA and/or ETB receptors on renal afferent nerves, and animals will be fed a high salt or high fat diet. Together, these studies will provide a mechanistic understanding of how excitation versus inhibition of renal afferent nerves contributes to hypertension and thus could lead to specific and efficient therapeutic interventions for the treatment of hypertension. This research study and the proposed mentored training plan will provide the applicant with the specific scientific training needed for successful transition into independence.


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: 2025 ( Subtotal = $161,689 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cardiovascular Diseases Research	000	5	8/22/2025	NON-COMPETING CONTINUATION	$161,689
														Subtotal = $161,689

Issue Date FY: 2024 ( Subtotal = $161,689 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cardiovascular Diseases Research	000	4	7/26/2024	NON-COMPETING CONTINUATION	$161,689
														Subtotal = $161,689

Issue Date FY: 2023 ( Subtotal = $161,689 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cardiovascular Diseases Research	000	3	8/3/2023	NON-COMPETING CONTINUATION	$161,689
														Subtotal = $161,689

Issue Date FY: 2022 ( Subtotal = $161,689 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cardiovascular Diseases Research	000	2	7/25/2022	NON-COMPETING CONTINUATION	$161,689
														Subtotal = $161,689

Issue Date FY: 2021 ( Subtotal = $161,689 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cardiovascular Diseases Research	000	1	8/27/2021	NEW	$161,689
														Subtotal = $161,689

Grand Total All Awards = $808,445

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Renal Sensory Nerve Contribution to Hypertension

Award Number: K01HL159047

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/27/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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