PMID- 24838176
OWN - NLM
STAT- MEDLINE
DCOM- 20140828
LR  - 20201209
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 115
IP  - 2
DP  - 2014 Jul 7
TI  - Stretch-activation of angiotensin II type 1a receptors contributes to the 
      myogenic response of mouse mesenteric and renal arteries.
PG  - 263-72
LID - 10.1161/CIRCRESAHA.115.302882 [doi]
AB  - RATIONALE: 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. 
      OBJECTIVE: 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. METHODS 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. CONCLUSIONS: 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.
CI  - (c) 2014 American Heart Association, Inc.
FAU - Schleifenbaum, Johanna
AU  - Schleifenbaum J
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Kassmann, Mario
AU  - Kassmann M
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Szijarto, Istvan Andras
AU  - Szijarto IA
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Hercule, Hantz C
AU  - Hercule HC
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Tano, Jean-Yves
AU  - Tano JY
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Weinert, Stefanie
AU  - Weinert S
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Heidenreich, Matthias
AU  - Heidenreich M
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Pathan, Asif R
AU  - Pathan AR
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Anistan, Yoland-Marie
AU  - Anistan YM
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Alenina, Natalia
AU  - Alenina N
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Rusch, Nancy J
AU  - Rusch NJ
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Bader, Michael
AU  - Bader M
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Jentsch, Thomas J
AU  - Jentsch TJ
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.).
FAU - Gollasch, Maik
AU  - Gollasch M
AD  - From the Medical Clinic for Nephrology and Internal Intensive Care, Charite 
      Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), 
      Berlin, Germany (J.S., M.K., I.A.S., H.C.H., J.-Y.T., Y.-M.A., M.G.); Max 
      Delbruck Center for Molecular Medicine, Berlin, Germany (S.W., M.H., N.A., M.B., 
      T.J.J.); Department Physiology and Pathology of Ion Transport, Leibniz-Institut 
      fur Molekulare Pharmakologie (FMP), Berlin, Germany (S.W., M.H., T.J.J.); 
      Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock (A.R.P., N.J.R.); and Broad Institute of MIT and Harvard, 
      Cambridge, MA (M.H.). maik.gollasch@charite.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140516
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone)
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Anthracenes)
RN  - 0 (KCNQ Potassium Channels)
RN  - 0 (KCNQ3 Potassium Channel)
RN  - 0 (KCNQ5 channel, mouse)
RN  - 0 (Kcnq3 protein, mouse)
RN  - 0 (Kcnq4 protein, mouse)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (TRPC6 Cation Channel)
RN  - 0 (Trpc6 protein, mouse)
RN  - BH3B64OKL9 (4-Aminopyridine)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - 4-Aminopyridine/pharmacology
MH  - Angiotensin II Type 1 Receptor Blockers/pharmacology
MH  - Animals
MH  - Anthracenes/pharmacology
MH  - GTP-Binding Protein alpha Subunits, Gq-G11/physiology
MH  - HEK293 Cells
MH  - Hemorheology
MH  - Humans
MH  - KCNQ Potassium Channels/physiology
MH  - KCNQ3 Potassium Channel/physiology
MH  - Losartan/pharmacology
MH  - Mesenteric Arteries/cytology/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocytes, Smooth Muscle/*physiology
MH  - Osmotic Pressure
MH  - Pressoreceptors/*physiology
MH  - Receptor, Angiotensin, Type 1/deficiency/genetics/*physiology
MH  - Renal Artery/cytology/*physiology
MH  - TRPC Cation Channels/physiology
MH  - TRPC6 Cation Channel
MH  - Transcription, Genetic
MH  - Vascular Resistance/drug effects/physiology
OTO - NOTNLM
OT  - GTP-binding protein alpha subunits, Gq-G11
OT  - KCNQ potassium channels
OT  - TRPC cation channels
OT  - angiotensin II
OT  - mice, transgenic
OT  - potassium channels
OT  - receptor, angiotensin, type 1
EDAT- 2014/05/20 06:00
MHDA- 2014/08/29 06:00
CRDT- 2014/05/20 06:00
PHST- 2014/05/20 06:00 [entrez]
PHST- 2014/05/20 06:00 [pubmed]
PHST- 2014/08/29 06:00 [medline]
AID - CIRCRESAHA.115.302882 [pii]
AID - 10.1161/CIRCRESAHA.115.302882 [doi]
PST - ppublish
SO  - Circ Res. 2014 Jul 7;115(2):263-72. doi: 10.1161/CIRCRESAHA.115.302882. Epub 2014 
      May 16.