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(Hypertension. 2009;53:654.)
© 2009 American Heart Association, Inc.

Original Articles

Heterogeneity of L- and T-Channels in the Vasculature

Rationale for the Efficacy of Combined L- and T-Blockade

Christine J. Ball; David P. Wilson; Stuart P. Turner; David A. Saint; John F. Beltrame

From the Cardiology Research Laboratory, Queen Elizabeth Hospital (C.J.B., D.P.W., S.P.T., J.F.B.), and Department of Physiology, School of Molecular and Biomedical Science (D.P.W., D.A.S., J.F.B.), University of Adelaide, Adelaide, Australia.

Correspondence to John F. Beltrame, Cardiology Research Laboratory, Queen Elizabeth Hospital, University of Adelaide, 28 Woodville Rd, Woodville South, SA 5011, Australia. E-mail john.beltrame{at}adelaide.edu.au

Clinical studies suggest that T-type Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ channel blocker responses in human microvessels; (3) incremental inhibition of constrictor responses with combined L- and T-Ca²⁺ channel blockers despite maximal L-channel blockade; (4) the use of structurally diverse Ca²⁺ channel blockers with varied affinity for L- and T-channels; (5) the use of pharmacodynamically and therapeutically appropriate Ca²⁺ 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.

Key Words: calcium • calcium channel blockers • vessels • vasoconstriction • vasculature

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Combined L-/T-Type Calcium Channel Blockers: Ready for Prime Time

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Hypertension 2009 53: 592-594. [Extract] [Full Text] [PDF]

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