Attenuated noradrenaline-induced contraction of pulmonary arteries from rats treated with monocrotaline: role of rho kinase.
Noradrenaline-induced pulmonary artery contraction was reduced in monocrotaline-treated rats. The possibility that this could be due to alterations in the rho kinase pathway was examined in this study. A combination of nifedipine (10(-6) M) and thapsigargin (10(-6) M) attenuated noradrenaline-induced contraction significantly more in artery segments from monocrotaline-treated rats than in artery segments from control rats indicating a reduced role for calcium sensitization in artery segments from monocrotaline-treated rats. In artery segments permeabilized with ionomycin, CaCl(2) (1.25 mmol/l) produced significantly greater contraction in monocrotaline treated rats compared with control rats. Addition of noradrenaline (10(-5) M) to the bath produced further contractions in both groups. However, noradrenaline-induced contraction was less in monocrotaline-treated rats compared with controls. Y-27632 concentration dependently relaxed ring segments of pulmonary artery pre-contracted with noradrenaline (10(-5)M). The pIC(50) values were 6.46+/- 0.09 (n=5) 5.81+/- 0.06 (n=5) in control and pulmonary hypertensive rings, respectively. The maximum relaxation to Y-27632 was significantly higher in monocrotaline-treated rats. ROCK II was the predominant isoform of rho kinase expressed in the pulmonary artery. The level of expression was increased in rats treated with monocrotaline. These results would suggest that while basal rho kinase activity was elevated in monocrotaline-induced pulmonary hypertension, noradrenaline-induced contraction was attenuated, suggesting poor coupling of the receptor activation to rho kinase activation.
Khan
Islam
I
Department of Biochemistry, Faculty of Medicine, Kuwait University, Safat, Kuwait.
Oriowo
Mabayoje A
MA
Chandrasekhar
Bindu
B
Kadavil
Elizabeth A
EA
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D014662:Vasoconstrictor Agents; C108830:Y 27632; D016686:Monocrotaline; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D002118:Calcium; D009638:Norepinephrine