Calcium channels and cation transport ATPases in cardiac hypertrophy induced by aortic constriction in newborn rats.
Cardiac enlargement due to gradual pressure overload was induced by abdominal aortic constriction in 2-day-old rats. On day 90, the functional performance of the left ventricle was assessed by acute load test (ligation of ascending aorta) in open-chest anaesthetized animals. Two subgroups, designated compensated and decompensated hypertrophy (CH and DH), were distinguished on the basis of the functional reserve of left ventricle, which was significantly impaired in DH but not in CH, and of right ventricle weight, which was markedly increased in DH but not significantly modified in CH. In total particulate fractions prepared from hypertrophied left ventricles, the levels (per g tissue) of sarcoplasmic reticulum Ca(2+)-transport systems were decreased, either slightly (by 13-16%: [3H]ryanodine binding) or moderately (by 28%: thapsigargin-sensitive Ca(2+)-ATPase activity). The number of sarcolemmal L-type Ca2+ channels ([3H]PN200-110 binding) was not modified significantly, while that of beta 1-adrenoceptors ([3H]CGP-12177 binding) was reduced, especially in the DH group (by 39%). Na+,K(+)-ATPase activity was reduced by 28% in CH and 41% in DH. [3H]Ouabain binding experiments (saturation and dissociation) indicated the existence of two high-affinity binding sites, attributable to the Na+, K(+)-ATPase alpha 3 and alpha 2 subunit isoforms; while the relatively minor alpha 3 component did not change significantly in hypertrophied ventricles, the alpha 2 component was markedly down-regulated, decreasing by 57% in CH and 82% in DH.
Zheng
L
L
Laboratoire de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium.
Wibo
M
M
Kolár
F
F
Godfraind
T
T
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001011:Aorta / Q000502:physiology*; D001665:Binding Sites; D015220:Calcium Channels / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D003250:Constriction; D017275:Isradipine / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010042:Ouabain / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000378:metabolism
D015220:Calcium Channels; D012433:Ryanodine; D010042:Ouabain; D017275:Isradipine