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Stretch‐activation of angiotensin II type 1a receptors contributes to the myogenic response of mouse mesenteric and renal arteries (1067.8)
Author(s) -
Schleifenbaum Johanna,
Kassmann Mario,
Szijártó István,
Hercule Hantz,
Weinert Stefanie,
Heidenreich Matthias,
Pathan Asif,
Anistan YolandMarie,
Alenitalia,
Rusch Nancy,
Bader Michael,
Jentsch Thomas,
Gollasch Maik
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1067.8
Subject(s) - trpc6 , mesenteric arteries , angiotensin ii , trpc , receptor , myogenic contraction , vasoconstriction , medicine , endocrinology , trpc3 , chemistry , transient receptor potential channel , vascular smooth muscle , microbiology and biotechnology , stretch activated ion channel , ion channel , biology , artery , voltage gated ion channel , smooth muscle
Wall stretch is a major stimulus for the myogenic response of small arteries to pressure. Recent findings suggest that G protein‐coupled receptors can elicit a stretch response. Our aim was to determine if angiotensin II type 1 receptors (AT1R) in vascular smooth muscle cells (VSMC) 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, TRPC6 channels or subtypes of the KCNQ (Kv7) gene family (KCNQ3, 4 or 5). We identified a mechano‐sensing mechanism in mesenteric arteries and the renal circulation that relies on coupling of the AT1R subtype a (AT1aR) to a Gq/11‐protein as a critical event to accomplish the myogenic response. The mechano‐activation occurs after block of AT1R, and in the absence of angiotensinogen or TRPC6. Activation of AT1aR suppresses XE991‐sensitive Kv channel currents in VSMCs, blocking these channels enhances mesenteric and renal myogenic tone. Although KCNQ3, 4 and 5 are expressed in VSMCs, XE991‐sensitive K+ current and myogenic contractions persist in arteries deficient in these channels. Our results provide evidence that myogenic responses of mouse mesenteric and renal arteries rely on ligand‐independent mechano‐activation of AT1aR. This signal relies on an ion channel distinct from TRPC6 or KCNQ3, 4 or 5. Grant Funding Source : Supported by Deutsche Forschungsgemeinschaft (DFG)