Evidence for a functional calcium-sensing receptor that modulates myogenic tone in rat subcutaneous small arteries.
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.
Ohanian
Jacqueline
J
University Dept. of Medicine, University of Manchester and Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. johanian@man.ac.uk
Gatfield
Kelly M
KM
Ward
Donald T
DT
Ohanian
Vasken
V
D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D001158:Arteries / Q000502:physiology*; D002118:Calcium / Q000493:pharmacokinetics; D020013:Calcium Signaling / Q000502:physiology; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000276:immunology / Q000378:metabolism*; D040521:Subcutaneous Tissue / Q000098:blood supply*; D014655:Vascular Resistance / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D044169:Receptors, Calcium-Sensing; D011493:Protein Kinase C; D008274:Magnesium; D002118:Calcium