May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Cell Signaling Mechanisms in the Myogenic Response in Retinal Arterioles: Roles of PKC and MAP Kinases
Author Affiliations & Notes
  • R. H. Rosa, Jr.
    Dept of Ophthalmology, Scott & White Eye Institute, Temple, Texas
  • T. W. Hein
    Dept of Ophthalmology, Scott & White Eye Institute, Temple, Texas
  • H. Liu
    Dept of Ophthalmology, Scott & White Eye Institute, Temple, Texas
  • W. Xu
    Dept of Ophthalmology, Scott & White Eye Institute, Temple, Texas
  • L. Kuo
    Systems Biology and Translational Medicine, Texas A&M Health Science Center, Temple, Texas
  • Footnotes
    Commercial Relationships  R.H. Rosa, None; T.W. Hein, None; H. Liu, None; W. Xu, None; L. Kuo, None.
  • Footnotes
    Support  NIH Grant K08EY016143, Scott & White Research Foundation, Kruse Family Centennial Endowment, Ophthalmic Vascular Research Program
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3264. doi:https://doi.org/
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      R. H. Rosa, Jr., T. W. Hein, H. Liu, W. Xu, L. Kuo; Cell Signaling Mechanisms in the Myogenic Response in Retinal Arterioles: Roles of PKC and MAP Kinases. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3264. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : It is well documented that tissue blood flow is closely regulated to match the metabolic need of a tissue via moment-by-moment adjustment of vessel tone by local vascular pressure (myogenic response) and tissue activities (metabolic response). However, the myogenic vasomotor activity in the retinal arterioles has not been systematically studied and the signaling mechanisms underlying this vasomotor regulation have not been identified. Recently, several investigators have suggested that activation of protein kinase C (PKC) and mitogen-activated protein (MAP) kinase signaling pathways mediates the myogenic response in skeletal muscle and heart tissues. However, the relative contribution of these signaling pathways to the myogenic response in retinal arterioles has not been elucidated.

Methods: : To directly characterize and determine the involved signaling molecules in the retinal myogenic response, second-order porcine retinal arterioles (70-120 µm in maximal diameter) were isolated, cannulated, and pressurized for in vitro study. The pressure-diameter relation was determined using videomicroscopic techniques. The myogenic response was characterized between 25 to 105 cmH2O intraluminal pressure in the absence or presence of specific inhibitor for PKC (chelerythrine, 3 µM) or p38 MAP kinase (SB-203580, 3 µM).

Results: : All isolated vessels developed basal tone at 36-37°C within 30-60 minutes at 55 cmH2O lumenal pressure. Lowering lumenal pressure below 45 cmH2O caused a reduction of vessel diameter. At pressures between 45 and 75 cmH2O, the retinal arterioles demonstrated myogenic activity with maintenance of a relatively constant lumenal diameter. Increasing intraluminal pressure above 75 cmH2O caused a passive distention of these vessels. In the presence of sodium nitroprusside (0.1 mM), all arterioles responded to pressure changes passively. The myogenic response was blocked by the PKC inhibitor chelerythrine and partially blocked by the p38 MAP kinase inhibitor SB-203580.

Conclusions: : We have demonstrated that second order retinal arterioles exhibit a moderate myogenic response by maintaining constant lumenal diameter within the range of physiological pressure. PKC, to a greater extent than p38 MAP kinase, appears to play a role in myogenic activity in the retinal arterioles. Greater understanding of how vasomotor function is regulated by intraluminal pressure may lead to new strategies to treat retinal vascular dysfunction associated with hypertension.

Keywords: signal transduction: pharmacology/physiology • blood supply • inhibitory receptors 
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