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Temporal effects of inflammation on the autonomic control of circulation during exercise in type 2 diabetic rats

Award Number: R01HL144723
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT A reflex arising from the contraction of hindlimb skeletal muscles is an important neural mechanism that is responsible for the cardiovascular adjustments to exercise. These adjustments, which include increases in peripheral vascular resistance, cardiac contractility and heart rate, function to increase arterial blood flow and oxygen to the exercising muscles, and in turn support their ability to contract. This neural mechanism has been named the exercise pressor reflex, and its afferent arm is comprised of group III and IV afferents whose endings are located in and near the muscle interstitium. Group III and IV afferents are commonly affected by diabetes which often results in peripheral neuropathy causing a range of problems from allodynia to hyperalgesia to hypoalgesia as the disease progresses. Chronic inflammation is one of the known mechanisms for peripheral neuropathy, directly affecting group III and IV afferents, and is present in diabetes, aging, and cardiovascular disease. The overall goal of the experiments proposed is to shed light on the role of pro-inflammatory cytokines on the exercise pressor reflex as diabetes progresses. In the proposed experiments, we will pay particular attention to two important pro-inflammatory cytokines known to be upregulated in diabetics and those with cardiovascular disease, namely interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). We will also pay particular attention to two important anti-inflammatory cytokines known to be downregulated in diabetics and those with cardiovascular disease, namely interleukin 10 (IL-10), and interleukin 4 (IL-4).We will examine in decerebrated, unanesthetized rats the pressor, cardioaccelerator, and sympathetic activity responses to static and intermittent contraction both before and during pharmacological blockade of the cytokine receptors. The proposed experiments will also quantify the potential up-regulation or down-regulation of these circulating cytokines using serum samples in multiplex assays. We anticipate that these experiments will provide new information about the role of pro- and anti-inflammatory cytokines in the progression of diabetes on the autonomic control of circulation during exercise.


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: 2023 ( Subtotal = $533,030 )
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Cardiovascular Diseases Research	001	5	1/14/2023	SUPPLEMENT FOR EXPANSION	$79,250
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Cardiovascular Diseases Research	000	5	12/20/2022	NON-COMPETING CONTINUATION	$408,402
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Cardiovascular Diseases Research	002	5	3/6/2023	NON-COMPETING CONTINUATION	$45,378
														Subtotal = $533,030

Issue Date FY: 2022 ( Subtotal = $490,252 )
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cardiovascular Diseases Research	000	4	12/15/2021	NON-COMPETING CONTINUATION	$441,226
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Cardiovascular Diseases Research	001	4	5/31/2022	NON-COMPETING CONTINUATION	$49,026
														Subtotal = $490,252

Issue Date FY: 2021 ( Subtotal = $430,662 )
2021	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cardiovascular Diseases Research	000	3	2/5/2021	NON-COMPETING CONTINUATION	$430,662
														Subtotal = $430,662

Issue Date FY: 2020 ( Subtotal = $559,504 )
2020	2020	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cardiovascular Diseases Research	001	2	12/20/2019	NON-COMPETING CONTINUATION	$531,529
2020	2020	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cardiovascular Diseases Research	002	2	1/31/2020	NON-COMPETING CONTINUATION	$27,975
2020	2019	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cardiovascular Diseases Research	000	1	11/19/2019	NEW	$0
														Subtotal = $559,504

Issue Date FY: 2019 ( Subtotal = $469,787 )
2019	2019	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cardiovascular Diseases Research	000	1	12/21/2018	NEW	$469,787
														Subtotal = $469,787

Grand Total All Awards = $2,483,235

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Temporal effects of inflammation on the autonomic control of circulation during exercise in type 2 diabetic rats

Award Number: R01HL144723

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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