PubMed:24838176 JSONTXT

{"project":"Allie","denotations":[{"id":"SS1_24838176_5_0","span":{"begin":406,"end":437},"obj":"expanded"},{"id":"SS2_24838176_5_0","span":{"begin":439,"end":443},"obj":"abbr"},{"id":"SS1_24838176_7_0","span":{"begin":718,"end":756},"obj":"expanded"},{"id":"SS2_24838176_7_0","span":{"begin":758,"end":763},"obj":"abbr"}],"relations":[{"id":"AE1_24838176_5_0","pred":"abbreviatedTo","subj":"SS1_24838176_5_0","obj":"SS2_24838176_5_0"},{"id":"AE1_24838176_7_0","pred":"abbreviatedTo","subj":"SS1_24838176_7_0","obj":"SS2_24838176_7_0"}],"text":"Stretch-activation of angiotensin II type 1a receptors contributes to the myogenic response of mouse mesenteric and renal arteries.\nRATIONALE: 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.\nOBJECTIVE: 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.\nMETHODS AND RESULTS: 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.\nCONCLUSIONS: 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."}