Cardiac calcineurin during transition from hypertrophy to heart failure in rats.
We studied an alteration of calcineurin expression in the heart and its modification by cyclosporin A and an ACE inhibitor, temocapril, using Dahl salt-sensitive (DS) rats with hypertensive left ventricular hypertrophy (LVH) and congestive heart failure (CHF). Calcineurin protein expression in the LV myocardium was increased in the LVH stage, but then decreased during CHF transition. Chronic cyclosporin A treatment (10 mg/kg/day), which inhibits calcineurin activity, could not block the increases of LV weight and dimensions and did not improve the LV systolic function during the CHF transition. In contrast, chronic temocapril treatment (20 mg/kg/day) restored the downregulation of calcineurin expression, but progression of the hypertrophic process was inhibited. Therefore, cardiac calcineurin is increased in the hypertensive LVH and may be involved in the development of the adaptive hypertrophic process. However, calcineurin expression is downregulated during CHF transition and may no longer play a major role in the pathogenesis of myocardial hypertrophy in the failing hearts.
Hayashida
W
W
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
Kihara
Y
Y
Yasaka
A
A
Sasayama
S
S
D000222:Adaptation, Physiological / Q000187:drug effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D004562:Electrocardiography; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006984:Hypertrophy / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D020303:Rats, Inbred Dahl; D013841:Thiazepines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D065095:Calcineurin Inhibitors; D013841:Thiazepines; D016572:Cyclosporine; C055603:temocapril hydrochloride; D019703:Calcineurin