title: Alterations in the inotropic responses to forskolin and Ca2+ and reduced gene expressions of Ca2+-signaling proteins induced by chronic volume overload in rabbits.
abstract: Volume overload results in eccentric cardiac hypertrophy, but it is still unknown how this mechanical overload modulates the inotropic response to exogenous Ca2+ or adenylyl cyclase stimulation. Inotropic responsiveness in vivo and the levels of gene expression of Ca2+ 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 CaCl2. Dose-related changes of LV+dP/dt to CaCl2 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+/Ca2+ exchanger, sarcoplasmic reticulum Ca2+-ATPase, and ryanodine receptor decreased significantly at 4 and 12 weeks in the volume-overload rabbits compared with the sham rabbits, but the mRNA levels of phospholamban and calsequestrin remained unchanged. Chronic volume overload alters contractile responsiveness to Ca2+ or adenylyl cyclase stimulation, and downregulation of steady state mRNA levels of Ca2+ signaling proteins might be, at least in part, related to this pathologic process.
authors: The First Department of Internal Medicine, Yamagata University School of Medicine, Japan.
authors: N
authors: N
authors: Takahashi
authors: H
authors: H
authors: Atsumi
authors: S
authors: S
authors: Nakada
authors: Y
authors: Y
authors: Takeishi
authors: H
authors: H
authors: Tomoike
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002122:Calcium Chloride / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis / Q000235:genetics; D002155:Calsequestrin / Q000096:biosynthesis / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis / Q000235:genetics; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis / Q000235:genetics; D000099211:Phospholamban
chemical_list: D002122:Calcium Chloride; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002155:Calsequestrin; D002316:Cardiotonic Agents; D005576:Colforsin; D018076:DNA, Complementary; D009124:Muscle Proteins; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban