Arteries are finely tuned thermosensors regulating myogenic tone and blood flow

Abstract

The smooth muscle cells surrounding small arteries and arterioles sense changes in local blood pressure and reflexively adjust their contractility to regulate vessel caliber. This autoregulatory property, known as myogenic tone, helps maintain a constant capillary pressure, which is important for tissue perfusion, fluid balance and vessel integrity. Here, we show that in addition to pressure, temperature is a critical determinant of myogenic tone. Heating steeply activates tone in mouse skeletal muscle, brain, gut, and skin arteries with a temperature co-efficient (Q10) of ~11-20, reflecting a highly thermosensitive process. Further, the temperatures for half-maximal tone correspond closely to resting tissue temperatures, indicating that arterial tone is sensitive to small thermal fluctuations. In skeletal muscle arteries, we show that temperature and intraluminal pressure are sensed largely independently yet integrated to trigger contractility. Further, we reveal key roles for heat-sensitive channels TRPV1 and TRPM4 in heat-induced myogenic tone in the skeletal muscle, both in vitro and in vivo. Elevations in temperature are known to increase tissue perfusion by altering blood viscosity; remarkably, we demonstrate that thermosensitive tone counterbalances this effect. Thus, the thermosensitivity of myogenic tone is tuned to tissue temperature and serves as a fundamental mechanism to regulate local blood flow.