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

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 α q/11 and/or G α 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  μ 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 α q/11 and G α 12 were abundantly expressed at the mRNA and protein levels in SMA . The G α q/11 inhibitor YM ‐254890 suppressed MT development, and the Phosholipase C inhibitors U73122 and ET ‐18‐ OCH 3 robustly inhibited it. We found an age‐dependent increase in ROCK 2 mRNA expression, and in basal MT . The specific ROCK 2 inhibitor KD 025 robustly inhibited MT in SMA s in all mice with an age‐dependent variation in KD 025 sensitivity. The inhibitory effect of KD 025 was not prevented by the L‐type Ca 2+ channel activator BayK 8644. KD 025 reversibly inhibited MT and endothelin‐1 vasoconstriction in small pial arteries from Göttingen minipigs. Conclusions: MT development in SMA s occurs through a G α q/11 / PLC /Ca 2+ ‐dependent pathway, and is maintained via ROCK 2‐mediated Ca 2+ sensitization. Increased MT at mature adulthood can be explained by increased ROCK 2 expression/activity.