Piezo proteins are transmembrane ion channels, specialized in detecting mechanosensitive stimuli and transduce mechanical forces into biochemical signals. Piezo proteins research has helped understand physiological mechanisms, but the integrative role that Piezo1 plays in the regulation of the microvasculature has remained unstudied. Our main objective was to characterize ex vivo microvascular responses to the blockade of Piezo1 mechanotransduction in male (n=29) and female (n=24) Sprague-Dawley (SD) rats. Gracilis arterioles (GA) and middle cerebral arterioles (MCA) were harvested for ex-vivo vessel preparations. After vessel viability confirmation, every vessel was submitted to myogenic and flow challenges under control conditions and after Grammostola Mechanotoxin 4 (GsMTx4) incubation to blocking Piezo1 channels, to quantify the homeostatic response of arterioles before and after Piezo1 antagonism. We are able to report Piezo1 as indispensable component in vascular smooth muscle cells (VSMC) and Endothelial cells (EC) to sense and change vessel diameter based on intravascular pressure and shear stress, correspondingly. Also, we report for the first time a heterogeneous response in males and females after Piezo1 antagonism in representative resistance arterioles from the skeletal muscle and cerebral circulation
