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|dc.identifier.citation||Hypertension, 2009; 53(4):654-660||-|
|dc.description||Copyright © 2009 American Heart Association, Inc.||-|
|dc.description.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.||-|
|dc.description.statementofresponsibility||Christine J. Ball, David P. Wilson, Stuart P. Turner, David A. Saint and John F. Beltrame||-|
|dc.publisher||Lippincott Williams & Wilkins||-|
|dc.subject||calcium channel blockers||-|
|dc.title||Heterogeneity of L- and T-channels in the vasculature: Rationale for the efficacy of combined L- and T-blockade||-|
|dc.identifier.orcid||Beltrame, J. [0000-0002-4294-6510]||-|
|Appears in Collections:||Aurora harvest|
Molecular and Biomedical Science publications
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