Dataset Information

Role of age, Rho-kinase 2 expression, and G protein-mediated signaling in the myogenic response in mouse small mesenteric arteries.

ABSTRACT: The myogenic response (MR) and myogenic tone (MT) in resistance vessels is crucial for maintaining peripheral vascular resistance and blood flow autoregulation. Development of MT involves G protein-coupled receptors, and may be affected by aging.

Aims

(1) to estimate the mesenteric blood flow in myogenically active small mesenteric arteries; (2) to investigate the signaling from G_?q/11 and/or G_?12 activation to MT development; (3) to investigate the role of Rho-kinase 2 and aging on MT in mesenteric resistance arteries.

Methods

we used pressure myography, quantitative real-time PCR, and immunolocalization to study small (<200 ?m) mesenteric arteries (SMA) from young, mature adult, and middle aged mice.

Results

Poiseuille flow calculations indicated autoregulation of blood flow at 60-120 mm Hg arterial pressure. G_?q/11 and G_?12 were abundantly expressed at the mRNA and protein levels in SMA. The G_?q/11 inhibitor YM-254890 suppressed MT development, and the Phosholipase C inhibitors U73122 and ET-18-OCH3 robustly inhibited it. We found an age-dependent increase in ROCK2 mRNA expression, and in basal MT. The specific ROCK2 inhibitor KD025 robustly inhibited MT in SMAs in all mice with an age-dependent variation in KD025 sensitivity. The inhibitory effect of KD025 was not prevented by the L-type Ca²⁺ channel activator BayK 8644. KD025 reversibly inhibited MT and endothelin-1 vasoconstriction in small pial arteries from Göttingen minipigs.

Conclusions

MT development in SMAs occurs through a G_?q/11 /PLC/Ca²⁺ -dependent pathway, and is maintained via ROCK2-mediated Ca²⁺ sensitization. Increased MT at mature adulthood can be explained by increased ROCK2 expression/activity.

SUBMITTER: Bjorling K

PROVIDER: S-EPMC6129776 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Role of age, Rho-kinase 2 expression, and G protein-mediated signaling in the myogenic response in mouse small mesenteric arteries.

Björling Karl K Joseph Philomeena D PD Egebjerg Kristian K Salomonsson Max M Hansen Jakob L JL Ludvigsen Trine P TP Jensen Lars J LJ

Physiological reports 20180901 17

The myogenic response (MR) and myogenic tone (MT) in resistance vessels is crucial for maintaining peripheral vascular resistance and blood flow autoregulation. Development of MT involves G protein-coupled receptors, and may be affected by aging.<h4>Aims</h4>(1) to estimate the mesenteric blood flow in myogenically active small mesenteric arteries; (2) to investigate the signaling from G<sub>αq/11</sub> and/or G<sub>α12</sub> activation to MT development; (3) to investigate the role of Rho-kinas ...[more]

PMID: 30198176

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Dataset Information

Role of age, Rho-kinase 2 expression, and G protein-mediated signaling in the myogenic response in mouse small mesenteric arteries.

Aims

Methods

Results

Conclusions

Publications

Role of age, Rho-kinase 2 expression, and G protein-mediated signaling in the myogenic response in mouse small mesenteric arteries.

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