Relaxant responses to calcium channel antagonists and potassium channel opener in human saphenous vein.
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) Ca(2+) 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 pIC(50) for nifedipine was significantly (8.20 +/- 0.05; n = 6; mean +/- SEM; P < 0.05) greater than in tissues contracted with > or =40 mm [K(+)](e). 3.-- Tissues contracted with 20 mm [K(+)](e) also relaxed in response to mibefradil (pIC(50) = 6.1 +/- 0.14) and pinacidil (pIC(50) = 6.45 +/- 0.08), the latter being almost completely reversed (93.4 +/- 9.9%) by addition of glibenclamide (10 microm). 4.-- The resting E(m) 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 E(m) to -82 +/- 0.6 mV (n = 52). 5.-- N(omega)-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 E(m) distinctly below the presumed threshold for the opening of the classic (Ca(V)1.3alpha(1)) L-type Ca(2+) channels, and (ii) did not depend on generation of nitric oxide.
Ford
C
C
Division of Basic Medical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St John's, NL, Canada A1B 3V6.
Bieger
D
D
Mong
K
K
Tabrizchi
R
R
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020747:Calcium Channels, T-Type / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D020748:Mibefradil / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists*; D012501:Saphenous Vein / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D015221:Potassium Channels; D014665:Vasodilator Agents; D020748:Mibefradil; D020110:Pinacidil; D009543:Nifedipine