Relaxant responses to calcium channel antagonists and potassium channel opener in human saphenous vein

• Published in: Autonomic & autacoid pharmacology Vol. 26; no. 1; pp. 7 - 13
• Main Authors: Ford, C., Bieger, D., Mong, K., Tabrizchi, R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2006
• Subjects: Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - drug effects; Calcium Channels, T-Type - drug effects; Dose-Response Relationship, Drug; excitation-contraction coupling; human vascular smooth muscle; Humans; In Vitro Techniques; L-type and T-type channels; membrane potential; Membrane Potentials; Mibefradil - pharmacology; Muscle, Smooth, Vascular - drug effects; Nifedipine - pharmacology; organic calcium channel antagonist; Pinacidil - pharmacology; potassium channels; Potassium Channels - agonists; Saphenous Vein - drug effects; Saphenous Vein - physiology; Vasodilation - drug effects; Vasodilator Agents - pharmacology
• ISSN: 1474-8665; 1474-8673
• DOI: 10.1111/j.1474-8673.2005.00352.x

Summary 1 As shown in a parallel study the magnitude of depolarization induced in human saphenous vein by raising external potassium ([K+]e) falls markedly below the theoretical values predicted by the Goldman–Hodgkin–Katz equations. This anomaly prompted us to re‐examine the relaxant actions of L‐type (nifedipine) and T‐type (mibefradil) Ca2+ channel antagonists, and relaxant and electrophysiological effects of the K+ channel opener, pinacidil, on saphenous veins contracted by the elevation of [K+]e. 2 Nifedipine produced concentration–dependent relaxations in tissues contracted at various high [K+]e. In tissues contracted with 20 mm [K+]e, the pIC50 for nifedipine was significantly (8.20 ± 0.05; n = 6; mean ± SEM; P < 0.05) greater than in tissues contracted with ≥40 mm [K+]e. 3 Tissues contracted with 20 mm [K+]e also relaxed in response to mibefradil (pIC50 = 6.1 ± 0.14) and pinacidil (pIC50 = 6.45 ± 0.08), the latter being almost completely reversed (93.4 ± 9.9%) by addition of glibenclamide (10 μm). 4 The resting Em of smooth muscle cells of saphenous vein was −77.0 ± 0.7 mV (n = 52), and 20 mm [K+]e produced a modest but significant depolarization to −73.0 ± 0.7 mV (n = 52). Incubation with pinacidil plus 20 mm [K+]e resulted in a significant hyperpolarization of the Em to −82 ± 0.6 mV (n = 52). 5 Nω‐nitro‐l‐arginine methyl ester did not impede the relaxant responses of nifedipine, mibefradil or pinacidil. 6 In conclusion, the relaxant effects of nifedipine and pinacidil (i) occurred at an Em distinctly below the presumed threshold for the opening of the classic (CaV1.3α1) L‐type Ca2+ channels, and (ii) did not depend on generation of nitric oxide.