Valsartan Restores Sarcoplasmic Reticulum Function With No Appreciable Effect on Resting Cardiac Function in Pacing-Induced Heart Failure

Autor: Masateru Kohno, Takahiro Tokuhisa, Masahiro Doi, Takeshi Yamamoto, Masafumi Yano, Shigeki Kobayashi, Shinichi Okuda, Masunori Matsuzaki, Tomoko Ohkusa, Tetsuro Oda
Rok vydání: 2004
Předmět:
Cardiac function curve
Tachycardia
medicine.medical_specialty
Angiotensin receptor
Heart disease
Drug Evaluation
Preclinical
Tetrazoles
Calcium-Transporting ATPases
Tacrolimus Binding Proteins
Norepinephrine
Dogs
Dobutamine
Physiology (medical)
Internal medicine
Receptors
Adrenergic
beta
Cyclic AMP
Animals
Medicine
Calcium Signaling
Phosphorylation
Heart Failure
Ventricular Remodeling
business.industry
Ryanodine receptor
Angiotensin II
Cardiac Pacing
Artificial
Ryanodine Receptor Calcium Release Channel
Valine
medicine.disease
Cyclic AMP-Dependent Protein Kinases
Myocardial Contraction
Sarcoplasmic Reticulum
Endocrinology
Valsartan
Heart failure
Tachycardia
Ventricular
Cardiology
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Angiotensin II Type 1 Receptor Blockers
Protein Processing
Post-Translational
medicine.drug
Zdroj: Circulation. 109:911-919
ISSN: 1524-4539
0009-7322
DOI: 10.1161/01.cir.0000115526.92541.d2
Popis: Background— Although angiotensin II receptor blockade is considered to be useful for the treatment of human heart failure, little beneficial hemodynamic effect has been shown in some experimental failing hearts. In this study, we assessed the effect of an angiotensin II receptor blocker, valsartan, on sarcoplasmic reticulum (SR) function, defectiveness of which is a major pathogenic mechanism in heart failure. Methods and Results— SR vesicles were isolated from dog left ventricular muscle (normal or exposed to 4-week rapid ventricular pacing with or without valsartan). In the untreated and valsartan-treated paced dogs, cardiac function showed similar deterioration (compared with before pacing). However, both the density of β-receptors and the contractile response to dobutamine were greater in the valsartan-treated paced dogs than in the untreated paced dogs. In untreated paced hearts, the ryanodine receptor was protein kinase A–hyperphosphorylated, showed an abnormal Ca 2+ leak, and had a decreased amount of ryanodine receptor–bound FKBP12.6. No such phenomena were seen in the valsartan-treated paced hearts. Both the SR Ca 2+ uptake function and the amount of Ca 2+ -ATPase were decreased in the untreated failing SR, but both were restored in the valsartan-treated SR. Conclusions— During the development of pacing-induced heart failure, valsartan preserved the density of β-receptors and concurrently restored SR function without improving resting cardiac function.
Databáze: OpenAIRE
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