Traumatic Brain Injury Alters PAQR7‐induced Vasorelaxation in Pressurized Cerebral Arteries

Abstract

Traumatic brain injury (TBI) induces acute changes in cerebrovascular function, including alterations to cerebral artery contractility, which ultimately increase the incidence of both ischemic and hemorrhagic events. Cerebrovascular tone is controlled by hormonal, neurogenic, endothelial, and myogenic responses. Progesterone, a steroid hormone, has been evaluated as a potential treatment to improve TBI outcome; however, progesterone has failed to translate to patient benefits in clinical trials, potentially due to its pleiotropic effects on multiple receptors. Progestin & adipoQ receptor 7 (PAQR7) is a plasma membrane progesterone receptor involved in the vasorelaxation of human blood vessels. However, little is known about the smooth muscle‐specific role of PAQR7 in resistance size cerebral arteries following TBI. Here, we examined PAQR7 function in pressurized endothelium‐denuded cerebral resistance size arteries 24 hours following moderately severe TBI (controlled cortical impact). Baseline myogenic tone of middle cerebral arteries (MCA) was attenuated following TBI. PAQR7‐induced vasorelaxation in pressurized MCA from TBI rats was attenuated in a concentration‐dependent manner as compared to sham controls (10−9M‐10−7M). Moreover, pre‐incubation with inhibitors of adenylyl cyclase (AC), PKA, or PKG attenuated PAQR7‐induced vasorelaxation in both groups. In conclusion, smooth muscle‐specific PAQR7 vasodilation involves an AC‐PKA/PKG pathway in cerebral resistance size arteries, and moderately severe TBI attenuates cerebral artery myogenic tone, which reduces overall arterial vasodilatory capacity.Support or Funding InformationSupported by The Florida State University Graduate School Dissertation Award Grant.