Myogenic Vasoconstriction Requires Canonical Gq/11 Signaling of Angiotensin II Type 1a Receptor in Murine Vasculature [article]

Yingqiu Cui, Mario Kassmann, Sophie Nickel, Chenglin Zhang, Natalia Alenina, Yoland Marie Anistan, Johanna Schleifenbaum, Michael Bader, Donald Gordon Welsh, Yu Huang, Maik Gollasch
2020 bioRxiv   pre-print
Angiotensin II (Ang II) type 1 receptors (AT1R) have been proposed to transduce myogenic vasoconstriction to keep blood flow constant in response to intravascular pressure increases. However, the AT1R subtype(s) involved and their downstream signaling pathways are still elusive. We used Agtr1a-/-, Agtr1b-/- and smooth muscle-specific (SM) AT1aR knockout mice, selective Gq/11 protein inhibitors, β-arrestin and Gq/11 signaling biased agonists to characterize the function of AT1Rs in the
more » ... of the myogenic response and possible downstream signaling cascades. Myogenic and Ang II-induced vasoconstrictions were diminished in perfused renal vasculature, isolated pressurized mesenteric and cerebral arteries of Agtr1a-/- and SM-Agtr1a mice but not Agtr1b-/- mice. The Gq/11 blocker FR900359 decreased myogenic tone and Ang II vasoconstrictions while selective biased targeting of AT1R non-canonical β-arrestin signaling pathways had no effects. We conclude that myogenic arterial constriction requires canonical Gq/11-dependent signaling pathways of mechanoactivated AT1aR in murine mesenteric, cerebral and renal circulation.
doi:10.1101/2020.09.09.289280 fatcat:lww2pzczanaitgkoq5jfaprdca