# TRPV1 channels in arterial smooth muscle: a novel vasoconstrictor mechanism to promote maintained cerebral blood flow during acute  decreases in blood pressure

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $507,062

## Abstract

Precise control of arterial diameter throughout the body is essential to maintain perfusion pressure and
blood flow to vital organs, such as the brain. Ca2+ influx through L-type voltage-dependent Ca2+ channels
(VDCCs) has traditionally been viewed as the major Ca2+ entry pathway in arterial smooth muscle (ASM) that
controls contraction and the regulation of arterial diameter. Here, we provide direct evidence for a second
major Ca2+ entry pathway in some types of ASM—the transient receptor potential vanilloid 1 (TRPV1) channel,
a “non-selective” Ca2+-permeable ion channel typically involved in nociception in sensory nerves. Using
“optical patch-clamping” techniques, we provide the first measurements of Ca2+ influx through single TRPV1
channels (“sparklets”). Importantly, our preliminary data also demonstrate engagement of ASM TRPV1
channels by activation of 1-adrenergic receptors (1-ARs)—the major vasoconstrictor pathway of the
sympathetic nervous system (SNS). The role of the SNS in maintaining cerebral blood flow (CBF) is particularly
important during episodes of acute hypotension (e.g., hemorrhagic shock) and is achieved in part through 1-
AR–mediated vasoconstriction in peripheral tissue. Our overarching hypothesis is that, in response to acute
decreases in blood pressure, constriction of non-brain arteries possessing ASM TRPV1 channels tunes vascular
resistance to redistribute blood to cerebral arteries, which we have found to lack TRPV1 channels.
 Within Aim 1, we explore the basis of TRPV1 activation by -ARs. The goal of this aim is to unravel the
linkages between 1-ARs, ASM TRPV1 channels, Ca2+ signaling and arterial diameter. We believe the
differential expression of TRPV1 and the activation of this channel by 1-AR ligands play important roles in the
regulation ASM Ca2+ and arterial diameter by the SNS. Specifically, we test the hypothesis that SNS-evoked
TRPV1 channel activation promotes increased global cytosolic Ca2+ and vasoconstriction via multiple pathways
including: 1) direct Ca2+ entry through TRPV1 channels and, 2) TRPV1-mediated cation influx, membrane
potential (VM) depolarization and enhanced VDCC activity. In Aim 2, we combine in vivo measurements of
arterial diameter, ASM Ca2+ and CBF to elucidate the role of TRPV1 channels in promoting the maintenance of
CBF during acute decreases in blood pressure that mimic hemorrhagic shock.
 In summary, this proposal is designed to provide unprecedented resolution of TRPV1 channel impact
on arterial diameter and CBF. Identifying a key role for ASM TRPV1 in promoting CBF during acute decreases
in blood pressure has the potential to provide a wealth of new information of great benefit to individual shock
patients and our society at large.

## Key facts

- **NIH application ID:** 9903431
- **Project number:** 5R01HL142888-02
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** GEORGE C WELLMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $507,062
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903431

## Citation

> US National Institutes of Health, RePORTER application 9903431, TRPV1 channels in arterial smooth muscle: a novel vasoconstrictor mechanism to promote maintained cerebral blood flow during acute  decreases in blood pressure (5R01HL142888-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9903431. Licensed CC0.

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