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

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Abstract
Myogenic tone of small arteries is dependent on the presence of extracellular calcium (![Formula][1]), 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 μm internal diameter) mounted in a pressure myograph with an intraluminal pressure of 70 mmHg were studied after the development of myogenic tone. Increasing ![Formula][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 μM) increased the responses to ![Formula][3] 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. [1]: /embed/tex-math-1.gif [2]: /embed/tex-math-2.gif [3]: /embed/tex-math-3.gif