Referenced in: none

Automatically associated channels: Kv7.3 , TRP , TRPC , TRPC6

Title: Stretch-Activation of Angiotensin II Type 1a Receptors Contributes to the Myogenic Response of Mouse Mesenteric and Renal Arteries.

Authors: Johanna Schleifenbaum, Mario Kassmann, István Szijártó, Hantz Hercule, Jean-Yves Tano, Stefanie Weinert, Matthias Heidenreich, Asif Pathan, Yoland Anistan, Natalia Alenina, Nancy Rusch, Thomas Jentsch, Michael Bader, Maik Gollasch

Journal, date & volume: Circ. Res., 2014 May 16 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24838176

Abstract
Vascular wall stretch is the major stimulus for the myogenic response of small arteries to pressure. The molecular mechanisms are elusive, but recent findings suggest that G protein-coupled receptors can elicit a stretch response.To determine whether angiotensin II type 1 receptors (AT1R) in vascular smooth muscle cells exert mechanosensitivity and identify the downstream ion channel mediators of myogenic vasoconstriction.We used mice deficient in AT1R signaling molecules and putative ion channel targets, namely AT1R, angiotensinogen, transient receptor potential channel 6 (TRPC6) channels, or several subtypes of the voltage-gated K+ (Kv7) gene family (KCNQ3, 4, or 5). We identified a mechanosensing mechanism in isolated mesenteric arteries and in the renal circulation that relies on coupling of the AT1R subtype a to a Gq/11 protein as a critical event to accomplish the myogenic response. Arterial mechanoactivation occurs after pharmacological block of AT1R and in the absence of angiotensinogen or TRPC6 channels. Activation of AT1R subtype a by osmotically induced membrane stretch suppresses an XE991-sensitive Kv channel current in patch-clamped vascular smooth muscle cells, and similar concentrations of XE991 enhance mesenteric and renal myogenic tone. Although XE991-sensitive KCNQ3, 4, and 5 channels are expressed in vascular smooth muscle cells, XE991-sensitive K+ current and myogenic contractions persist in arteries deficient in these channels.Our results provide definitive evidence that myogenic responses of mouse mesenteric and renal arteries rely on ligand-independent, mechanoactivation of AT1R subtype a. The AT1R subtype a signal relies on an ion channel distinct from TRPC6 or KCNQ3, 4, or 5 to enact vascular smooth muscle cell activation and elevated vascular resistance.