title: Inhibition by quinine of endothelium-dependent relaxation of rabbit aortic strips.
abstract: 1 The effects of quinine sulphate, tetramethylammonium chloride (TMA) and tetraethylammonium chloride (TEA) (all blockers of the Ca2+-activated K+ channels) on the relaxations induced by acetylcholine (ACh), calcium ionophore A23187 and sodium nitrite were studied in helical strips of rabbit aorta. 2 The strips were contracted to a moderate stable tone with phenylephrine (10(-7) M). ACh (4 X 10(-9) to 10(-6) M) as well as A23187 (10(-8) to 3 X 10(-7) M) reduced this tone in a concentration- and endothelium-dependent manner. 3 Pretreatment of the tissues with quinine (2.5 X 10(-5) to 10(-4) M) for 60 min produced a concentration-dependent inhibition of the relaxation induced by ACh. Also 90 min incubation of the strips with TMA (3 X 10(-3) to 6.5 X 10(-2) M) or TEA (10(-3) to 3 X 10(-2) M) inhibited the ACh-evoked relaxation in a manner similar to quinine. 4 Quinine (10(-4) M, 60 min), TMA (6.5 X 10(-2) M, 90 min) or TEA (3 X 10(-2) M, 90 min) produced 5 to 10 fold reductions in the relaxant EC50 values of A23187 and ACh and depressed (by 40 to 95%) the maximal relaxations to the ionophore and ACh. 5. On a molar basis, quinine was more effective than the two tetraalkylammonium ions in reducing the endothelium-dependent relaxations of the aortic strips induced by ACh or A23187. The inhibitory actions were reversible after 60 to 90 min washout. 6. Exposure of the strips to either quinine (10-4M, 60 min), TMA (6.5 x 10-2 M, 90 min) or TEA (3 X 10-2 M, 90 min), however, did not influence significantly the relaxations evoked by sodium nitrite, a direct smooth muscle relaxant. 7. These results suggest that stimulation of the Ca2+-activated K' channels could be, at least partially, responsible for the endothelium-dependent relaxations induced by ACh or A23 187. Their activation might not be required for the endothelium-independent relaxant effects of sodium nitrite.
authors.affiliation: Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, H-1445, Hungary.
authors.forename: D
authors.initials: D
authors.lastname: Gebremedhin
authors.forename: P
authors.initials: P
authors.lastname: Hadházy
authors.forename: K
authors.initials: K
authors.lastname: Magyar
mesh_terms: D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001464:Barium / Q000494:pharmacology; D017609:Barium Compounds; D000001:Calcimycin / Q000494:pharmacology; D002712:Chlorides; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology*; D011817:Rabbits; D012977:Sodium Nitrite / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D000631:Aminopyridines; D017609:Barium Compounds; D002712:Chlorides; D000644:Quaternary Ammonium Compounds; D013757:Tetraethylammonium Compounds; C024986:barium chloride; D001464:Barium; D000001:Calcimycin; D011803:Quinine; D015761:4-Aminopyridine; C027917:tetramethylammonium; D012977:Sodium Nitrite