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

被引：17

作者：

Chennupati, Ramesh ^{[1
]}

Wirth, Angela ^{[2
]}

Favre, Julie ^{[3
]}

Li, Rui ^{[1
]}

Bonnavion, Remy ^{[1
]}

Jin, Young-June ^{[1
]}

Wietelmann, Astrid ^{[4
]}

Schweda, Frank ^{[5
]}

Wettschureck, Nina ^{[1
,6
,7
]}

Henrion, Daniel ^{[3
]}

Offermanns, Stefan ^{[1
,6
,7
]}

机构：

[1] Max Planck Inst Heart & Lung Res, Dept Pharmacol, Bad Nauheim, Germany

[2] Heidelberg Univ, Inst Pharmacol, Heidelberg, Germany

[3] Univ Angers, INSERM 1083, UMR CNRS 6015, Lab MITOVASC, Angers, France

[4] Max Planck Inst Heart & Lung Res, Sci Serv Grp Nucl Magnet Resonance Imaging, Bad Nauheim, Germany

[5] Univ Regensburg, Inst Physiol, Regensburg, Germany

[6] JW Goethe Univ Frankfurt, Med Fac, Ctr Mol Med, Frankfurt, Germany

[7] German Ctr Cardiovasc Res DZHK, Berlin, Germany

来源：

ELIFE | 2019年 / 8卷

关键词：

PROTEIN-COUPLED RECEPTORS; RHO-KINASE INHIBITION; SMOOTH-MUSCLE; SIGNALING MECHANISMS; CARDIAC-HYPERTROPHY; POTENTIAL CHANNELS; CA2+ SENSITIVITY; BLOOD-PRESSURE; EMERGING ROLE; TONE;

D O I：

10.7554/eLife.49374

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

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 G(12)/G(13) 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 G(12)/G(13)- 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.

引用

页数：21