# Control of microvascular function by ion channels

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $23,408

## Abstract

Activation of post-junctional neurotransmitter receptors in vascular smooth muscle cells modulates vascular tone
and causes significant alterations in organ perfusion, mechanisms of which may be amplified or reduced in
cardiovascular and renal disease. Neurotransmitter release from presynaptic nerve terminals is highly dependent
on extracellular Ca2+ influx. Thus, modulation of Ca2+-permeable channels in neurons that impinge on microvessels
can alter microcirculation by regulating neurotransmission. A large body of literature has elucidated the role of
vascular smooth muscle and endothelial cell Ca2+ signaling in the control of microvascular function. However, there
remains a significant knowledge gap on the function and pathophysiology of perivascular nerve ion channels in
microcirculation. The current application stems from pilot studies that uncovered a new role for the transient
receptor potential melastatin 8 (TRPM8) channels outside of sensory signaling. We propose an intriguing concept
that a subset of peripheral sympathetic nerves (sn) expresses TRPM8 channels. Our data suggest that snTRPM8
is redox-sensitive and that the responses mediated by perivascular snTRPM8 channels alter vascular resistance
via smooth muscle cell adrenergic system. We will use a repertoire of physiological; pharmacological; and high-
content imaging approaches to study the central hypothesis that snTRPM8 activation increases vascular
resistance and reduces vascular bed perfusion via Ca2+-dependent catecholamine neurotransmission and that
this pathway contributes to oxidative stress-induced vascular dysfunction. To address this hypothesis, three
specific aims will be investigated. Aim 1 will test the hypothesis that perivascular snTRPM8 activation reduces
microcirculation via sn-dependent vasoconstriction. Aim 2 will study the hypothesis that redox-evoked snTRPM8
channel activation increases vascular resistance. Aim 3 will explore the concept that snTRPM8-dependent
sympathoexcitation contributes to oxyradical-induced vascular dysfunction and renal damage. This project will
utilize selective pharmacological modulators of TRPM8 channels and mice with global and sn-specific TRPM8
deletion. Techniques to investigate microcirculation include transit-time ultrasound, laser-Doppler, and multiphoton
microscopy.

## Key facts

- **NIH application ID:** 10201230
- **Project number:** 3R01HL151735-01S1
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Adebowale Adebiyi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $23,408
- **Award type:** 3
- **Project period:** 2020-12-22 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201230

## Citation

> US National Institutes of Health, RePORTER application 10201230, Control of microvascular function by ion channels (3R01HL151735-01S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10201230. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*