# Cardiac sympathetic afferent reflex control of venous function

> **NIH NIH R01** · UNIVERSITY OF SOUTH DAKOTA · 2020 · $362,854

## Abstract

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.

## Key facts

- **NIH application ID:** 9852369
- **Project number:** 5R01HL136741-04
- **Recipient organization:** UNIVERSITY OF SOUTH DAKOTA
- **Principal Investigator:** DOUGLAS S MARTIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $362,854
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852369

## Citation

> US National Institutes of Health, RePORTER application 9852369, Cardiac sympathetic afferent reflex control of venous function (5R01HL136741-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9852369. Licensed CC0.

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