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

  • 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.
Author:Ramesh Chennupati, Angela Wirth, Julie Favre, Rui Li, Remy Bonnavion, Young-June Jin, Astrid Wietelmann, Frank Schweda, Nina WettschureckORCiDGND, Daniel Henrion, Stefan OffermannsORCiDGND
Pubmed Id:
Parent Title (English):eLife
Publisher:eLife Sciences Publications
Place of publication:Cambridge
Contributor(s):Mark T. Nelson
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/09/24
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2020/03/11
Tag:Cell biology; G-protein; Research article; Rho/Rho-kinase; human biology and medicine; mouse; myogenic tone; myogenic vasoconstriction; signal transduction; vascular smooth muscle
Page Number:21
First Page:1
Last Page:21
Copyright Chennupati et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0