Myogenic vasoconstriction requires G12/G13 and LARG to maintain local and systemic vascular resistance

eLife

Daniel Henrion¹  Stefan Offermanns²  Ramesh Chennupati³  Rémy Bonnavion³  Rui Li³  Young-June Jin³  Nina Wettschureck³  Angela Wirth⁴  Frank Schweda⁵  Julie Favre⁶  Astrid Wietelmann⁷ 

[1]Centre for Molecular Medicine, Medical Faculty, JW Goethe University Frankfurt, Frankfurt, Germany

[2]German Center for Cardiovascular Research (DZHK), Berlin, Germany

[3]Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany

[4]Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany

[5]Institute of Physiology, University of Regensburg, Regensburg, Germany

[6]Laboratoire MITOVASC, UMR CNRS 6015 - INSERM 1083, Université d'Angers, Angers, France

[7]Scientific Service Group Nuclear Magnetic Resonance Imaging, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany

关键词: myogenic vasoconstriction;    vascular smooth muscle;    G-protein;    Rho/Rho-kinase;    myogenic tone;    signal transduction;   

DOI  :  10.7554/eLife.49374

来源: DOAJ

【 摘 要 】

Myogenic vasoconstriction is an autoregulatory function of small arteries. Recently, G-protein-coupled receptors have been involved in myogenic vasoconstriction, but the downstream signalling mechanisms and the in-vivo-function of this myogenic autoregulation are poorly understood. Here, we show that small arteries from mice with smooth muscle-specific loss of G12/G13 or the Rho guanine nucleotide exchange factor ARHGEF12 have lost myogenic vasoconstriction. This defect was accompanied by loss of RhoA activation, while vessels showed normal increases in intracellular [Ca2+]. In the absence of myogenic vasoconstriction, perfusion of peripheral organs was increased, systemic vascular resistance was reduced and cardiac output and left ventricular mass were increased. In addition, animals with defective myogenic vasoconstriction showed aggravated hypotension in response to endotoxin. We conclude that G12/G13- and Rho-mediated signaling plays a key role in myogenic vasoconstriction and that myogenic tone is required to maintain local and systemic vascular resistance under physiological and pathological condition.

【 授权许可】

Unknown