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Type: Journal article
Title: Heterogeneity of L- and T-channels in the vasculature: Rationale for the efficacy of combined L- and T-blockade
Author: Smith, C.
Wilson, D.
Turner, S.
Saint, D.
Beltrame, J.
Citation: Hypertension, 2009; 53(4):654-660
Publisher: Lippincott Williams & Wilkins
Issue Date: 2009
ISSN: 0194-911X
Statement of
Christine J. Ball, David P. Wilson, Stuart P. Turner, David A. Saint and John F. Beltrame
Abstract: Clinical studies suggest that T-type Ca(2+) channel blockade may have incremental benefits over conventional L-channel blockade, particularly in microvascular disorders. This study examined functional vasomotor differences in L- and T-channel blockade between large and small vessels and compared the abundance of the L- and T-type channels in these vessels. The inhibition of endothelin-1 and potassium-induced vascular contractile responses by L-channel blockers (verapamil and nifedipine) was compared with combined L- and T-channel blockers (mibefradil and efonidipine) in large (rat aorta) and small (rat mesenteric and human subcutaneous) vessels using wire myography. All 4 of the Ca(2+) channel blockers inhibited contractile responses to a similar extent in large rat vessels; however, in rat microvessels, the combined L- and T-channel blockers produced significantly greater inhibition of contraction than L-channel blockers alone. The significance of this differential T-channel effect in microvessels was further supported by the following: (1) a greater abundance of T-channels compared with L-channels in microvessels but not in large vessels; (2) demonstration of divergent Ca(2+) channel blocker responses in human microvessels; (3) incremental inhibition of constrictor responses with combined L- and T-Ca(2+) channel blockers despite maximal L-channel blockade; (4) the use of structurally diverse Ca(2+) channel blockers with varied affinity for L- and T-channels; (5) the use of pharmacodynamically and therapeutically appropriate Ca(2+) channel blocker concentrations; (6) confirmation of contractile agonist independent responses; and (7) exclusion of an endothelium-dependent mechanism. We propose that T-type channels play an important role in regulating contractile responses in the microvasculature and, therefore, are a potential therapeutic target.
Keywords: calcium
calcium channel blockers
Description: Copyright © 2009 American Heart Association, Inc.
DOI: 10.1161/HYPERTENSIONAHA.108.125831
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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