Alpha 1-adrenoceptor subtypes mediating noradrenaline-induced contraction of pulmonary artery from pulmonary hypertensive rats.
The effect of monocrotaline-induced pulmonary hypertension on alpha(1)-adrenoceptor-mediated contractions of pulmonary artery segments was studied. In control and monocrotaline-treated rats, noradrenaline evoked concentration-dependent contractions of the pulmonary artery. There was no change in the potency and affinity of noradrenaline but the maximum response and receptor reserve were significantly reduced. Noradrenaline-induced contractions were competitively antagonized by prazosin, 2-(2-6dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride (WB 4101) and 8-[2-[4-(2methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9 dione dihydrochloride (BMY 7378) with pA(2) values of 9.64+/-0.16, 9.45+/-0.10 and 8.30+/-0.14, respectively. These antagonists also competitively antagonized noradrenaline-induced contractions of pulmonary artery segments isolated from rats with monocrotaline-induced pulmonary hypertension. The pA(2) values were 9.66+/-0.11 (prazosin), 9.62+/-0.09 (WB 4101) and 8.47+/-0.15 (BMY 7378). Chloroethylclonidine (CEC) shifted noradrenaline concentration-response curve to the right and depressed the maximum response. There was no difference between the effects of CEC in both groups. It was therefore concluded that pulmonary hypertension significantly reduced noradrenaline-induced contractions of the rat pulmonary artery without affecting the sensitivity. Studies with receptor-selective antagonists confirmed that alpha(1)D-adrenoceptor subtype is the predominant receptor subtype in the pulmonary artery and this was maintained in this disease state.
Oriowo
Mabayoje A
MA
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, P.O. Box 24923, 13110 Safat, Kuwait. Oriowo@hsc.kuniv.edu.kw
Chandrasekhar
Bindu
B
Kadavil
Elizabeth A
EA
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D016686:Monocrotaline; D009638:Norepinephrine; D011224:Prazosin