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Cardiac sympathetic afferent reflex control of venous function

Award Number: R01HL136741
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2022

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Cardiac sympathetic afferent reflex control of venous function - Hypertension afflicts about 33% of the adult population and is antecedent to myocardial infarction, heart failure, stroke, and renal disease which contribute to 1 in 3 deaths. This problem is growing. The American Heart Association predicts that by 2030 hypertension prevalence will increase by 8%. Hypertension control was suggested as a public health initiative with one of the greatest impacts on mortality. Despite increased awareness and current therapies, hypertension control remains suboptimal in 50% of patients indicating the need for new paradigms in blood pressure control. Our group and others showed that venous tone and cardiopulmonary volume were increased in hypertensive animals and humans which contribute to hypertension initiation and maintenance. Yet, the venous compartment remains largely unexplored as a target to control blood pressure, in large part due to fragmented knowledge about mechanisms outside of the baroreceptors that control venous tone. Our ultimate goal is to advance the field by revealing novel mechanisms controlling venous tone and their dysregulation in disease (e.g. hypertension). This project tests the concepts that cardiac sympathetic afferent neural reflexes control venous function via the hypothalamic paraventricular nucleus (PVN) and that pathological over activity of this pathway leads to augmented venoconstriction that contributes to the initiation and maintenance of hypertension. Specific Aim I will define the extent to which cardiac sympathetic afferents control venous tone, cardiac filling, cardiac output and blood pressure. Our work identified the PVN as a brain site regulating venous tone. Specific Aim II will determine whether the PVN plays a critical role in cardiac sympathetic afferent control of venous tone. Dysregulation of afferent signaling pathways are often overlooked as triggers for cardiovascular disease. Specific aim III will test the hypothesis that over activity of the cardiac sympathetic afferent reflex contributes to enhanced venoconstriction and interruption of this mechanism attenuates hypertension. Collectively we expect this project to establish that the cardiac sympathetic afferent reflex is novel mechanism for controlling venous tone, cardiac filling and blood pressure. Dysregulation of this venous control mechanism contributes to venoconstriction in hypertension and that interruption of this mechanism reduces venous tone and high blood pressure. These studies will provide an important foundation for future work studying the cardiac sympathetic afferent reflex as a novel therapeutic target for conditions where venous return is abnormal.


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: 2022 ( Subtotal = $0 )
2022	2020	UNIVERSITY OF SOUTH DAKOTA	414 E CLARK ST	VERMILLION	SD	57069	CLAY	USA	Cardiovascular Diseases Research	000	4	6/17/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $362,854 )
2020	2020	THE UNIVERSITY OF SOUTH DAKOTA	414 E CLARK ST	VERMILLION	SD	57069	CLAY	USA	Cardiovascular Diseases Research	000	4	2/12/2020	NON-COMPETING CONTINUATION	$362,854
														Subtotal = $362,854

Issue Date FY: 2019 ( Subtotal = $363,075 )
2019	2019	THE UNIVERSITY OF SOUTH DAKOTA	414 E CLARK ST	VERMILLION	SD	57069	CLAY	USA	Cardiovascular Diseases Research	000	3	1/20/2019	NON-COMPETING CONTINUATION	$363,075
														Subtotal = $363,075

Issue Date FY: 2018 ( Subtotal = $363,286 )
2018	2018	THE UNIVERSITY OF SOUTH DAKOTA	414 E CLARK ST	VERMILLION	SD	57069	CLAY	USA	Cardiovascular Diseases Research	000	2	1/11/2018	NON-COMPETING CONTINUATION	$356,020
2018	2018	THE UNIVERSITY OF SOUTH DAKOTA	414 E CLARK ST	VERMILLION	SD	57069	CLAY	USA	Cardiovascular Diseases Research	001	2	6/23/2018	NON-COMPETING CONTINUATION	$7,266
														Subtotal = $363,286

Issue Date FY: 2017 ( Subtotal = $363,487 )
2017	2017	THE UNIVERSITY OF SOUTH DAKOTA	414 E CLARK ST	VERMILLION	SD	57069	CLAY	USA	Cardiovascular Diseases Research	000	1	2/1/2017	NEW	$363,487
														Subtotal = $363,487

Grand Total All Awards = $1,452,702

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Cardiac sympathetic afferent reflex control of venous function

Award Number: R01HL136741

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2022

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