Chloride channels and alpha1-adrenoceptor-mediated pulmonary artery smooth muscle contraction: effect of pulmonary hypertension.
Noradrenaline induced concentration-dependent contractions of pulmonary artery segments from control and monocrotaline-treated rats. There was a significant decrease in the maximum response but not sensitivity in artery segments from monocrotaline-treated rats. At a concentration (10(-6) M) that abolished KCl-induced contraction, nifedipine attenuated but did not abolish, noradrenaline-induced contraction in both groups. However, noradrenaline-induced contraction in artery segments from pulmonary hypertensive rats was more susceptible to inhibition by nifedipine. Bumetanide (10(-4) M), a chloride transport inhibitor and niflumic acid, a chloride channel inhibitor, reduced noradrenaline-induced contraction of the pulmonary artery in control and pulmonary hypertensive groups. These compounds were more effective in ring segments from pulmonary hypertensive rats. It was concluded that activation of chloride channels was involved in noradrenaline-induced contraction and that the contribution of chloride channels was enhanced in pulmonary hypertensive rats.
Oriowo
Mabayoje A
MA
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, PO Box 24923, 13110, Safat, Kuwait. Oriowo@hsc.edu.kw
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D007537:Isometric Contraction; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009544:Niflumic Acid / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011042:Poisons / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D049994:Sodium Potassium Chloride Symporter Inhibitors
D002121:Calcium Channel Blockers; D018118:Chloride Channels; D027963:Chloride-Bicarbonate Antiporters; D011042:Poisons; D018340:Receptors, Adrenergic, alpha-1; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide; D009544:Niflumic Acid; D016686:Monocrotaline; D009543:Nifedipine; D009638:Norepinephrine