TY  - JOUR
A1  - Chennupati, Ramesh
A1  - Wirth, Angela
A1  - Favre, Julie
A1  - Li, Rui
A1  - Bonnavion, Remy
A1  - Jin, Young-June
A1  - Wietelmann, Astrid
A1  - Schweda, Frank
A1  - Wettschureck, Nina
A1  - Henrion, Daniel
A1  - Offermanns, Stefan
T1  - Myogenic vasoconstriction requires G12/G13 and LARG to maintain local and systemic vascular resistance
T2  - eLife
N2  - 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.
KW  - Research article
KW  - Cell biology
KW  - human biology and medicine
KW  - myogenic vasoconstriction
KW  - vascular smooth muscle
KW  - G-protein
KW  - Rho/Rho-kinase
KW  - myogenic tone
KW  - signal transduction
KW  - mouse
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51836
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-518360
SN  - 2050-084X
N1  - 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.
VL  - 8
IS  - e49374
SP  - 1
EP  - 21
PB  - eLife Sciences Publications
CY  - Cambridge
ER  -