Effects of calcium channel antagonists and pertussis toxin on noradrenaline-induced contractions in pulmonary artery from pulmonary hypertensive rats.
The influence of calcium channel antagonists, felodipine and cadmium, as well as pertussis toxin on noradrenaline-induced contractions in pulmonary artery rings from rats with pulmonary hypertension induced by monocrotaline (MCT) were examined. MCT-treated rats had pulmonary hypertension, right ventricular hypertrophy and lung oedema, as compared to corresponding vehicle-treated rats. The MCT-treated animals did not have polycythemia as compared to vehicle-treated rats. Pre-treatment of pulmonary artery rings from MCT-treated rats with felodipine and cadmium significantly reduced the maximum response without altering the EC50 or the Hill coefficient of concentration-response curve to noradrenaline. In pulmonary artery rings from vehicle-treated rats, felodipine significantly increased the EC50 and reduced the maximum response and the Hill coefficient of the concentration-response curve to noradrenaline. In contrast, cadmium did not alter these parameters in pulmonary artery rings from vehicle-treated rats. Pertussis toxin did not affect noradrenaline-induced contractions in pulmonary artery rings from vehicle- or MCT-treated rats. Felodipine, cadmium and pertussis toxin were ineffective in inhibiting noradrenaline-induced contractions in aortic rings from either vehicle- or MCT-treated rats. Our results can be interpreted to indicate that alteration to voltage operated, felodipine-sensitive, calcium channels as well as, cadmium-sensitive sites contribute to the changes observed in the functional behavior of pulmonary blood vessels from pulmonary hypertensive rats.
D000818:Animals; D001011:Aorta / Q000503:physiopathology; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015736:Felodipine / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology*; D037342:Pertussis Toxin; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D010566:Virulence Factors, Bordetella; D002104:Cadmium; D016686:Monocrotaline; D037342:Pertussis Toxin; D015736:Felodipine; D009638:Norepinephrine