# NIH grant: Neural Control of Ventricular-Vascular Interactions During Exercise in Hypertension (1R01HL180465-01A1) — retained record

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[original source ↗](https://reporter.nih.gov/project-details/1R01HL180465-01A1)

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NIH grant 1R01HL180465-01A1: Neural Control of Ventricular-Vascular Interactions During Exercise in Hypertension
Institute: {'code': 'HL', 'abbreviation': 'NHLBI', 'name': 'National Heart Lung and Blood Institute', 'admin_org_id': '12500068', 'admin_funding_url': ''}. PI: Joseph T Mannozzi. Award: $773282.
Start: 2026-09-05T00:00:00.
Hypertension (HT) is one of the leading causes of cardiovascular related morbidity and mortality 
currently effecting 1 in 2 individuals in the U.S. with an enhanced prevalence in African Americans 
and post-menopausal females. Limitations in exercise capacity, and poor blood pressure control 
during exercise are common symptoms of HT that lead to enhanced risk of major cardiac events such 
as stroke and sudden cardiac arrest. In HT excessive sympathetic activation causes exaggerated 
vasoconstriction of peripheral vascular beds and even vasoconstriction in the coronary vasculature. 
This results in impaired myocardial oxygen delivery limiting ventricular function and restrains 
increases in cardiac output required to maintain skeletal muscle perfusion during exercise. The 
mechanisms by which this enhanced sympathetically-mediated vasocontraction occurs in HT is not well 
understood. In this proposal we are focused on expanding our investigations of the neural control 
of cardiovascular function to elucidate the mechanisms mediating enhanced sympathetic activation 
during exercise in HT. We propose that this occurs as a result of activation of multiple regional 
afferent neurons that impair the ability to raise cardiac output and maintain skeletal muscle 
perfusion. We hypothesize that in addition to coronary vasoconstriction, poor ventricular-vascular 
interactions, impaired central blood volume mobilization, and diastolic dysfunction contribute to 
the inability to raise cardiac output during exercise in HT. Poor skeletal muscle perfusion due to 
stifled increases in cardiac output will activate sensitized TRPV1 receptors on skeletal muscle 
afferents engendering systemic vasoconstriction of even the skeletal muscle itself amplifying 
existing afferent responses to under-perfusion causing positive feedback loop amplification of 
sympathetic activity. Furthermore, limitations in myocardial oxygen delivery as a result of 
coronary vasoconstriction, and potentially poor myocardial oxygen handling by mitochondria, during 
exercise in HT will activate cardiac sympathetic afferents thereby enhancing sympatho-excitation 
which amplifies the skeletal muscle afferent responses. To evaluate these integrative hypotheses, 
we will utilize our highly complex chronically instrumented conscious canine model to evaluate 
these altered ventricular-vascular interactions in HT using a longitudinal approach with each 
animal serving as its own control. Our long-term goal is to determine the mechanisms mediating 
heightened sympathetic responses during exercise in HT and determine the functional consequences of 
these responses in cardiovascular control. One of the unique strengths of this proposal is our 
ability to measure and analyze multiple hemodynamic variables in real time at rest and during 
exercise in the same animals before and after induction of HT. These studies will provide highly 
translational, longitudinal data and concepts regarding the mechanisms mediating exaggerated 
sympathetic vasoconstriction during exercise in HT and will provide potential therapeutic avenues 
for the prevention of exercise intolerance and major cardiac events such as stroke and sudden 
cardiac arrest during exercise.
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