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The Human Cardiovascular Control: The Role of Limb Veins

Award Number: R01HL144781
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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The Human Cardiovascular Control: The Role of Limb Veins - Project Summary/Abstract In this project, we examine the role venous distention plays in the reflex regulation of blood pressure. Our prior work in humans demonstrates that vascular distension of peripheral limb veins evokes a powerful sympathoexcitatory reflex (venous distension reflex, VDR) that raises blood pressure. In this proposal, we have three specific aims: 1) we will determine the role played by cyclooxygenase metabolites of arachidonic acid in evoking the VDR, and examine how prostaglandins mediate their effects on the VDR in humans. Based on our supportive pilot data, we hypothesize that acute blockade of cyclooxygenase enzyme system will markedly attenuate muscle sympathetic nerve activity (MSNA) and arterial pressure responses to limb venous distention; 2) we will examine the hypothesis that limb venous distension increases the gain and resets the operating point of the baroreflex system in healthy subjects. We speculate that these changes in the gain and operating point of the baroreflex can buffer blood pressure changes during orthostatic challenge; We will also examine if the interaction between VDR and baroreflex differs in males and females; and 3) we will examine the role VDR plays in maintaining blood pressure during orthostatic stress in human subjects. We hypothesize that the strength of the VDR and/or the interaction between the VDR and the baroreflex will be related to orthostatic tolerance. We also hypothesize that individuals with “orthostatic hypertension” will have a heightened VDR. We further speculate that maneuvers to reduce venous pooling in legs will attenuate the increase in blood pressure during orthostatic challenge in these subjects. The concepts to be studied challenge the prevailing “conventional wisdom” regarding how blood pressure is regulated during orthostatic stress. If the proposed aims are achieved, we will gain insight into the mechanisms by which venous distension evokes sympathoexcitation, how the VDR interacts with the baroreflex, and how this reflex contributes to blood pressure control during orthostatic stress.


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 = $0 )
2025	2023	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Cardiovascular Diseases Research	000	5	6/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $533,395 )
2023	2023	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Cardiovascular Diseases Research	001	5	5/7/2023	NON-COMPETING CONTINUATION	$533,395
2023	2022	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Cardiovascular Diseases Research	000	4	11/24/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $533,395

Issue Date FY: 2022 ( Subtotal = $533,395 )
2022	2022	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Cardiovascular Diseases Research	000	4	6/13/2022	NON-COMPETING CONTINUATION	$533,395
														Subtotal = $533,395

Issue Date FY: 2021 ( Subtotal = $533,395 )
2021	2021	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Cardiovascular Diseases Research	000	3	5/17/2021	NON-COMPETING CONTINUATION	$533,395
														Subtotal = $533,395

Issue Date FY: 2020 ( Subtotal = $533,395 )
2020	2020	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY DR C1607	HERSHEY	PA	17033	DAUPHIN	USA	Cardiovascular Diseases Research	000	2	5/15/2020	NON-COMPETING CONTINUATION	$533,395
														Subtotal = $533,395

Issue Date FY: 2019 ( Subtotal = $541,395 )
2019	2019	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY DR C1607	HERSHEY	PA	17033	DAUPHIN	USA	Cardiovascular Diseases Research	000	1	6/14/2019	NEW	$541,395
														Subtotal = $541,395

Grand Total All Awards = $2,674,975

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The Human Cardiovascular Control: The Role of Limb Veins

Award Number: R01HL144781

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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