| Summary: | Piezo1 proteins are Na+ and Ca2+ permeable mechanosensitive ion channels. Expressed on endothelial cell membranes, where they sense the shear stress forces created by blood flow, Piezo1 channels are essential for vascular development. The functional significance of vascular Piezo1 channels in adult physiology and pathology, however, remains largely unexplored. Therefore, using an inducible, endothelial-specific Piezo1 knock-out mouse line this study sought to identify and investigate the functional role of this channel in adult arterial vessels. Four morphologically and physiologically distinct arteries, the aorta, mesenteric, saphenous and carotid arteries, were selected and their responses to the vasoconstrictor phenylephrine (PE) and the vasorelaxant acetylcholine (ACh) were assessed using wire myography. While loss of endothelial Piezo1 did not alter or had only a small effect on the overall sensitivity or responsiveness of these vessels to either PE or ACh, further investigation revealed a significant increase in the endothelium-derived hyperpolarizing factor (EDHF) component of ACh-induced relaxation in mesenteric arteries. This anti-EDHF effect of Piezo1 was vascular bed specific, no difference between control or knock-out mice being observed in saphenous or carotid arteries. This finding led to the identification of a flow-stimulated vasoconstriction response in mesenteric vessels and furthermore provided an explanation for the reduced elevation in blood pressure detected in endothelial Piezo1 knock-out mice during exercise. Mesenteric arteries contract during exercise, enabling blood to be directed to tissues actively involved in physical movement. The data support the hypothesis that Piezo1 channels have specific importance in whole body physical exercise, sensing increased blood flow at the endothelium to elevate tone in the underlying vascular smooth muscle cells of visceral arteries, thus redirecting blood to the muscles.
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