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 Gαq/11 and/or Gα12 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 μm) 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. Gαq/11 and Gα12 were abundantly expressed at the mRNA and protein levels in SMA. The Gαq/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 Gαq/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.
Highlights
The myogenic response is a property possessed by resistance arteries
Since we are utilizing this preparation as a generic model for the myogenic response, we were interested in to what extent the myogenic response in this vascular bed is capable of autoregulating the blood flow
As Rho-kinase is crucially involved in the myogenic response in rat middle cerebral arteries (Gokina et al 2005; Jarajapu and Knot 2005) and skeletal muscle resistance arteries (Bolz et al 2003), and since it is the Rock2 determination (ROCK2) isoform that is involved in vascular smooth muscle cells (VSMCs) contractility (Wang et al 2009), we evaluated the role of ROCK2 in the aging-induced increases in myogenic tone (MT)
Summary
The myogenic response is a property possessed by resistance arteries. It is defined as an increase in vascular tone that follows a raise in transmural pressure, or as a decrease in vascular tone that follows a decline in transmural pressure (Schubert and Mulvany 1999). The second function, “autoregulation of flow and pressure” means that the myogenic response plays a central role in the preservation of a steady perfusion of the vasculature during changes in blood pressure Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society
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