EDHF-mediated vasodilatation appears to require the activation of endothelial IKCa and SKCa channels in order to promote smooth muscle hyperpolarization and subsequent vasodilatation. The role of endothelial [Ca2+] in this mechanism appears to be as the principal physiological activator of those channels. Therefore, factors that significantly affect the endothelial [Ca2+] response should be able to variably modulate IKCa and SKCa channel activation, and thus EDHF-mediated vasorelaxation.
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5. Chen, G. F., and Suzuki, H. (1990). Calcium dependency of the endothelium-dependent hyperpolarization in smooth muscle cells of the rabbit carotid artery. J. Physiol (Lond) 421, 521-534. This article first described the role of endothelial Ca2+ in EDHF-mediated smooth muscle hyperpolarization.
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7. Marrelli, S. P. (2001). Mechanisms of endothelial P2Y(1)- and P2Y(2)-mediated vasodilatation involve differential [Ca2+] responses. Am. J. Physiol. Heart Circ. Physiol. 281, H1759-H1766. This article provided direct evidence for an endothelial Ca2+ threshold for initiating EDHF-mediated vasodilatation.
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10. Knot, H. J., Lounsbury, K. M., Brayden, J. E., and Nelson, M. T. (1999). Gender differences in coronary artery diameter reflect changes in both endothelial Ca2+ and ecNOS activity. Am. J. Physiol. 276, H961-H969.
11. Marrelli, S. P., Eckmann, M. S., and Hunte, M. S. (2003). Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations. Am. J. Physiol Heart Circ. Physiol. 285, H1590-H1599. This article demonstrates the importance of endothe-lial Ca2+ as the physiological stimulus for endothelial hyperpolarization via activation of endothelial KCa channels.
12. Marrelli, S. P. (2002). Altered endothelial Ca2+ regulation following ischemia/reperfusion produces potentiated endothelium-derived hyperpolarizing factor-mediated dilations. Stroke 33, 2285-2291.
Dr. Marrelli is an assistant professor in the Department of Anesthesiol-ogy at Baylor College of Medicine where he studies endothelial regulation of vascular tone. In particular, Dr. Marrelli's research focuses on the blood vessels of the cerebral circulation and the effects of ischemia/reperfusion (or stroke) on subsequent vascular function.
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