# cAMP signaling in vascular smooth muscle in health and disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $653,647

## Abstract

Abstract .
The second messenger 3',5'-cyclic adenosine monophosphate (cAMP) is essential for regulating vascular
smooth muscle (VSM) function, including reactivity. The dogma that cAMP signaling in VSM only mediates
relaxation was recently challenged by our observation that glucose induces a subtle cAMP synthesis that
promotes contraction. These results suggest that cAMP versatility to regulate VSM reactivity to diverse stimuli
depends on their spatially confined properties within the cell, of which little is known. Moreover, no studies have
examined how cAMP pools are modulated by biological sex and its functional implications in VSM in health and
disease. Studies here will therefore address these key knowledge gaps. By leveraging the use of a sophisticated
toolkit in human and mouse VSM, exciting preliminary data is generated in support of the central hypothesis that
the production of discrete cAMP pools is essential for integrating receptor-dependent cAMP signaling to control
VSM reactivity in health and disease, and this is dependent on biological sex. This hypothesis will be tested in
three specific aims. Aim 1 is to test the hypothesis that Gs protein-coupled receptors (GsPCRs) induce sex-
specific discrete cAMP pools in VSM. Aim 2 is to test the hypothesis that GsPCRs cellular segregation triggers
distinct sex-specific discrete cAMP pools in VSM. Finally, Aim 3 is to test the hypothesis that discrete cAMP
pools in VSM are disrupted in diabetes and hypertension (HTN). The proposal has high basic, translational and
clinical significance as it will reveal 1) new insight into discrete cAMP pools in VSM, 2) their influence by biological
sex in health and disease, and 3) opportunities to identify novel targets and develop new therapeutic strategies.

## Key facts

- **NIH application ID:** 10370716
- **Project number:** 1R01HL161872-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Manuel F Navedo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $653,647
- **Award type:** 1
- **Project period:** 2021-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370716

## Citation

> US National Institutes of Health, RePORTER application 10370716, cAMP signaling in vascular smooth muscle in health and disease (1R01HL161872-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10370716. Licensed CC0.

---

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