Evidence for a functional calcium-sensing receptor that modulates myogenic tone in rat subcutaneous small arteries

Am J Physiol Heart Circ Physiol. 2005 Apr;288(4):H1756-62. doi: 10.1152/ajpheart.00739.2004. Epub 2004 Dec 2.

Abstract

Myogenic tone of small arteries is dependent on the presence of extracellular calcium (Ca(o)(2+)), and, recently, a receptor that senses changes in Ca(2+), the calcium-sensing receptor (CaR), has been detected in vascular tissue. We investigated whether the CaR is involved in the regulation of myogenic tone in rat subcutaneous small arteries. Immunoblot analysis using a monoclonal antibody against the CaR demonstrated its presence in rat subcutaneous arteries. To determine whether the CaR was functionally active, segments of artery (< 250 microm internal diameter) mounted in a pressure myograph with an intraluminal pressure of 70 mmHg were studied after the development of myogenic tone. Increasing Ca(o)(2+) concentration ([Ca(2+)](o)) cumulatively from 0.5 to 10 mM induced an initial constriction (0.5-2 mM) followed by dilation (42 +/- 5% loss of tone). The dose-dependent dilation was mimicked by other known CaR agonists including magnesium (1-10 mM) and the aminoglycosides neomycin (0.003-10 mM) and kanamycin (0.003-3 mM). PKC activation with the phorbol ester phorbol-12,13-dibutyrate (20nM) inhibited the dilation induced by high [Ca(2+)](o) or neomycin, whereas inhibition of PKC with GF109203X (10 microM) increased the responses to Ca(o)(2+) or neomycin, consistent with the role of PKC as a negative regulator of the CaR. We conclude that rat subcutaneous arteries express a functionally active CaR that may be involved in the modulation of myogenic tone and hence the regulation of peripheral vascular resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / pharmacology
  • Animals
  • Antibodies, Monoclonal
  • Arteries / physiology*
  • Calcium / pharmacokinetics
  • Calcium Signaling / physiology
  • Immunohistochemistry
  • MAP Kinase Signaling System / physiology
  • Magnesium / pharmacology
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Smooth, Vascular / physiology*
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcium-Sensing / immunology
  • Receptors, Calcium-Sensing / metabolism*
  • Subcutaneous Tissue / blood supply*
  • Vascular Resistance / physiology
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal
  • Receptors, Calcium-Sensing
  • Protein Kinase C
  • Magnesium
  • Calcium