Alterations in the Inotropic Responses to Forskolin and Ca^<2+> and Reduced Gene Expressions of Ca^<2+>-Signaling Proteins Induced by Chronic Volume Overload in Rabbits

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Volume overload results in eccentric cardiac hypertrophy, but it is still unknown how this mechanical overload modulates the inotropic response to exogenous Ca^<2+> or adenylyl cyclase stimulation. Inotropic responsiveness in vivo and the levels of gene expression of Ca^<2+> signaling proteins were studied in rabbit hearts hypertrophied as a result of volume overload at 4 and 12 weeks after arteriovenous shunt formation. In sham-operated control rabbits, left ventricular (LV) +dP/dt was augmented in response to graded doses of CaCl_2. Dose-related changes of LV+dP/dt to CaCl_2 were attenuated significantly in shunt rabbits with volume overload. Forskolin dose-dependently augmented LV+dP/dt in sham rabbits, which was also attenuated significantly in rabbits with volume overload. The mRNA levels of dihydropyridine receptor, Na+/Ca^<2+> exchanger, sarcoplasmic reticulum Ca^<2+>-ATPase, and ryanodine receptor decreased significantly at 4 and 12 weeks in the volume-overload rabbits compared with the sham rabbits, but them RNA levels of phospholamban and calsequestrin remained unchanged. Chronic volume overload alters contractile responsiveness to Ca^<2+> or adenylyl cyclase stimulation, and downregulation of steady state mRNA levels of Ca^<2+> signaling proteins might be, at least in part, related to this pathologic process.
社団法人日本循環器学会の論文
2000-10-20