Artery Like Smooth Muscle Drives Contractile Function in Dural Venous Sinuses

Abstract

The dural venous sinuses are the main conduit for cerebral blood flow to drain from the head back to the heart. Pathology of these sinuses has significant impacts on cerebral blood volume and intracranial pressure, indicating that these veins have an important role in cerebral hemodynamics. Active and modifiable mechanisms of sinus diameter control may present an opportunity for physiological or pathological regulation of venous blood flow. Here, we characterized the molecular and anatomical properties of dural vascular smooth muscle cells (SMCs) using RNA-sequencing and immunohistochemistry, demonstrating that artery-like SMCs are exclusive to sinus vessels. An ex vivo pressurized sinus preparation from mice was used to functionally characterize the vasodynamics of the sinus and its corresponding bridging veins. We found that the sinus contains dynamically contractile SMCs and constricts to both pressure and contractile agonists, while the bridging veins do not. We further demonstrated that these sinus SMCs exhibit dynamic calcium signaling that is responsive to contractile stimuli. These results reveal a contractile SMC phenotype localized to dural venous sinuses and demonstrate that sinus vessels possess active, artery-like mechanisms for regulating cerebral venous outflow.