Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 288, Issue 4, Pages H1756-H1762Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00739.2004
Keywords
vascular smooth muscle; magnesium; aminoglycosides; contractility; peripheral vascular resistance
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Myogenic tone of small arteries is dependent on the presence of extracellular calcium (Ca-o(2+)), and, recently, a receptor that senses changes in Ca2+, 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 mu m 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 ([Ca2+](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 [Ca2+](o) or neomycin, whereas inhibition of PKC with GF109203X (10 mu M) 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.
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