Chennupati, Ramesh and Wirth, Angela and Favre, Julie and Li, Rui and Bonnavion, Remy and Jin, Young-June and Wietelmann, Astrid and Schweda, Frank and Wettschureck, Nina and Henrion, Daniel and Offermanns, Stefan (2019) Myogenic vasoconstriction requires G(12)/G(13) and LARG to maintain local and systemic vascular resistance. ELIFE, 8: e49374. ISSN 2050-084X,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-COUPLED RECEPTORS; RHO-KINASE INHIBITION; SMOOTH-MUSCLE; SIGNALING MECHANISMS; CARDIAC-HYPERTROPHY; POTENTIAL CHANNELS; CA2+ SENSITIVITY; BLOOD-PRESSURE; EMERGING ROLE; TONE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Mar 2020 10:01 |
| Last Modified: | 27 Mar 2020 10:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26222 |
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