PT  - JOURNAL ARTICLE
AU  - Thieu X. Phan
AU  - Hoai T. Ton
AU  - Hajnalka Gulyás
AU  - Róbert Pórszász
AU  - Attila Tóth
AU  - Rebekah Russo
AU  - Matthew W. Kay
AU  - Niaz Sahibzada
AU  - Gerard P. Ahern
TI  - TRPV1 in arteries enables a rapid myogenic tone
AID  - 10.1101/2021.02.25.432719
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.25.432719
4099  - http://biorxiv.org/content/early/2021/02/27/2021.02.25.432719.short
4100  - http://biorxiv.org/content/early/2021/02/27/2021.02.25.432719.full
AB  - Arterioles maintain blow flow by adjusting their diameter in response to changes in local blood pressure. In this process called the myogenic response, a vascular smooth muscle mechanosensor controls tone predominantly through altering the membrane potential. In general, myogenic responses occur slowly, reaching a plateau in minutes. In the heart and skeletal muscle, however, myogenic tone is rapid; activation occurs in tens of seconds and arterial constrictions or raised extravascular pressure as brief as 100 ms remove tone. Previously, we identified extensive expression of TRPV1 in the smooth muscle of arterioles supplying skeletal muscle, heart and the adipose. Here we reveal a critical role for TRPV1 in the myogenic tone of these tissues. TRPV1 antagonists dilated skeletal muscle arterioles in vitro and in vivo, increased coronary flow in isolated hearts, and transiently decreased blood pressure. All of these effects of TRPV1 antagonists were abolished by genetic disruption of TRPV1. Stretch of isolated vascular smooth muscle cells, or raised intravascular pressure in arteries (with or without endothelium), triggered Ca2+ signaling and vasoconstriction. The majority of these stretch-responses were TRPV1-mediated, with the remaining tone being inhibited by the TRPM4 antagonist, 9-phenantrol. Notably, tone developed more quickly in arteries from wild-type compared with TRPV1-null mice. Furthermore, the rapid vasodilation following brief constriction of arterioles was also dependent on TRPV1, consistent with a rapid deactivation or inactivation of TRPV1. Pharmacologic experiments revealed that membrane stretch activates a phospholipase C/protein kinase C signaling pathway to activate TRPV1, and in turn, L-type Ca2+ channels. These results suggest a critical role, for TRPV1 in the dynamic regulation of myogenic tone and blood flow in the heart and skeletal muscle.Competing Interest StatementThe authors have declared no competing interest.