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 ab dominal aortic constriction in 2-day-old rats. On day 90, the function al 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 an d DH), were distinguished on the basis of the functional reserve of le ft ventricle, which was significantly impaired in DH but not in CH, an d of right ventricle weight, which was markedly increased in DH but no t significantly modified in CH. In total particulate fractions prepare d from hypertrophied left ventricles, the levels (per g tissue) of sar coplasmic reticulum Ca2+-transport systems were decreased, either slig htly (by 13-16%: [H-3]ryanodine binding) or moderately (by 28%: thapsi gargin-sensitive Ca2+-ATPase activity). The number of sarcolemmal L-ty pe Ca2+ channels ([H-3]PN200-110 binding) was not modified significant ly, while that of beta 1-adrenoceptors ([H-3]CGP-12177 binding) was re duced, especially in the DH group (by 39%). Na+,K+-ATPase activity was reduced by 28% in CH and 41% in DH. [H-3]Ouabain binding experiments (saturation and dissociation) indicated the existence of two high-affi nity binding sites, attributable to the Na+,K+-ATPase alpha 3 and alph a 2 subunit isoforms; while the relatively minor alpha 3 component did not change significantly in hypertrophied ventricles, the alpha 2 com ponent was markedly downregulated, decreasing by 57% in CH and 82% in DH.