Relaxant responses to calcium channel antagonists and potassium channel opener in human saphenous vein
| Autor: | Reza Tabrizchi, Kam Mong, Carol Ann Ford, Detlef Bieger |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Potassium Channels
Calcium Channels L-Type Nifedipine Vasodilator Agents In Vitro Techniques Pharmacology Muscle Smooth Vascular Membrane Potentials Calcium Channels T-Type chemistry.chemical_compound medicine Humans Saphenous Vein Mibefradil Dose-Response Relationship Drug Pinacidil Calcium channel Depolarization Hyperpolarization (biology) Calcium Channel Blockers Potassium channel Vasodilation chemistry Anesthesia Potassium channel opener medicine.drug |
| Zdroj: | Autonomic and Autacoid Pharmacology. 26:7-13 |
| ISSN: | 1474-8673 1474-8665 |
| Popis: | 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; P0.05) greater than in tissues contracted withor =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. |
| Databáze: | OpenAIRE |
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