Sex-dependent cAMP signaling domains in vascular smooth muscle

The ubiquitous second messenger 3’,5’ monophosphate (cAMP) is essential for regulating vascular smooth muscle (VSM) function. Despite the overwhelming number of studies examining cAMP signaling compartmentalization in multiple cell types, no study has examined how biological sex regulates discrete cAMP pools and the functional implications in VSM. In this study, cAMP biosensors targeted to the cytosol (cyt), plasm membrane (PM), and sarcoplasmic reticulum (SR) were used to examine subcellular cAMP domains using live-cell FRET imaging. We uncovered a sex-specific distribution of cAMP signaling domains where cAMP pools are constrained in the SR of male but not in female mice. To test whether sexually dimorphic cAMP pools are mediated by sex hormones, we used WT male and sham or ovariectomized (OVX) WT female mice. cAMP subcellular distribution was like that of males in VSM from OVX female mice. Interestingly, aortic rings from males and OVX females showed less relaxation responses to isoproterenol compared to sham females. Our study highlights sex-dependent segregation cAMP pools in VSM that could contribute to the sex-specific regulation of vascular reactivity. American Heart Association award 852984 Research Supplement to Promote Diversity in Science 23DIVSUP1069345. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.