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1 University Department of Medicine, University of Manchester, Manchester, United Kingdom
2 Biological Sciences, University of Manchester, Manchester, United Kingdom
* To whom correspondence should be addressed. E-mail: johanian{at}man.ac.uk.
Myogenic tone of small arteries is dependent on the presence of extracellular calcium (Ca2+ o) and recently a receptor that senses changes in Ca2+, the calcium-sensing receptor (CaR), has been detected in vascular tissue. We have investigated whether the CaR is involved in 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 70mmHg were studied following the development of myogenic tone. Increasing [Ca2+]o cumulatively from 0.5 - 10mM induced an initial constriction (0.5-2mM) followed by dilation (42±5% loss of tone). The dose-dependent dilation was mimicked by other known CaR agonists including magnesium (1-10mM) and the aminoglycosides neomycin (0.003-10mM) and kanamycin (0.003-3mM). Protein kinase C (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 (10µM) increased the responses to Ca2+o 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 modulation of myogenic tone and hence regulation of peripheral vascular resistance.
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