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Gustatory and interoceptive regulation of hypertension

Award Number: F31HL162540
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Gustatory and interoceptive regulation of hypertension - PROJECT SUMMARY The overconsumption of sodium (Na+) is a major health problem in the U.S. and around the world, having been linked to many health conditions, including hypertension—a major risk factor for cardiovascular disease. While the relationship between Na+-intake and hypertension is widely recognized, the mechanism(s) behind this relationship are not well understood. The proposed experiments aim to delineate the mechanism(s) underlying this relationship by investigating sensory systems that regulate Na+-taste/intake and blood pressure (BP). My preliminary studies conducted in mice discovered that neurons within the nodose and petrosal ganglion that express the angiotensin type 1a receptor (NPGAT1aR) send afferents to the nucleus of the solitary tract (NTS). The NPG contains neurons that function as baroreceptors that sense blood pressure or as gustatory afferents that transduce Na+-taste. Intriguingly, optogenetic excitation of afferents in the NTS arising from NPGAT1aR significantly reduces blood pressure and Na+-intake. Moreover, mice overconsuming NaCl solutions and rendered hypertensive via deliver of deoxycorticosterone acetate (DOCA-salt) required greater frequencies of stimulation to lower blood pressure relative to normotensive mice. Collectively, my preliminary results suggest that the NPGAT1aR send afferents to the NTS that mediate the interoception of blood pressure and the perception of Na+-taste and the excitability of these neurons can be used to study the etiology of hypertension that follows Na+ overconsumption. Accordingly, I have developed the overall hypothesis that NPGAT1aR send afferents to the NTS that regulate blood pressure and Na+-intake, and that AT1aR(s) on these neurons contribute to the development of DOCA- salt hypertension. To confirm or refute this hypothesis, I will address the following aims. Aim 1 will use neuroanatomical characterizations and optogenetic activation of NPGAT1aR afferents in the rostral and caudal NTS to determine whether the connectivity and excitation of these afferents are sufficient to alter Na+-intake and blood pressure under basal conditions and following depletion of blood volume. Aim 2 will use Cre-LoxP system and virally-mediated gene transfer to selectively delete AT1aR(s) from the NPG to determine whether these AT1aR are necessary for increased Na+-intake and decreased baroreflex sensitivity that accompany the DOCA-salt model of hypertension. Collectively, these experiments will shed light on gustatory and interoceptive integration in the brainstem to better understand the relationship between Na+-intake and blood pressure regulation, thereby providing novel insight that can be leveraged to develop treatments for 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: 2024 ( Subtotal = -$12,691 )
2024	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Cardiovascular Diseases Research	000	2	10/27/2023	NON-COMPETING CONTINUATION	-$10,822
2024	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Cardiovascular Diseases Research	001	2	9/23/2024	NON-COMPETING CONTINUATION	-$1,869
														Subtotal = -$12,691

Issue Date FY: 2023 ( Subtotal = $39,514 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Cardiovascular Diseases Research	001	2	3/31/2023	NON-COMPETING CONTINUATION	$942
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Cardiovascular Diseases Research	000	2	11/17/2022	NON-COMPETING CONTINUATION	$38,572
														Subtotal = $39,514

Issue Date FY: 2022 ( Subtotal = $38,572 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Cardiovascular Diseases Research	000	1	11/29/2021	NEW	$37,856
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Cardiovascular Diseases Research	001	1	11/29/2021	NEW	$0
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Cardiovascular Diseases Research	002	1	6/24/2022	NEW	$716
														Subtotal = $38,572

Grand Total All Awards = $65,395

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Gustatory and interoceptive regulation of hypertension

Award Number: F31HL162540

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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