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

¹University Department of Medicine, University of Manchester and Manchester Royal Infirmary, and ²Biological Sciences, University of Manchester, Manchester, United Kingdom

Submitted 22 July 2004 ; accepted in final form 30 November 2004

Myogenic tone of small arteries is dependent on the presence of extracellular calcium (), 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 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 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.

vascular smooth muscle; magnesium; aminoglycosides; contractility; peripheral vascular resistance

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