Mechanical load-dependent cardiac ER stress in vitro and in vivo: effects of preload and afterload.

Proteins are folded in the endoplasmic reticulum (ER). ER stress initially leads to compensatory upregulation of ER chaperones and later to apoptosis, but the contribution of biomechanical load vs. neurohumoral stress to myocardial ER stress is unknown.

Elevated afterload, neuroendocrine stimulation, and human heart failure increase BNP levels and inhibit preload-dependent SERCA upregulation.

Background: In heart failure, brain-type natriuretic peptide (BNP) is elevated and the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) downregulated. We previously showed that preload-induced SERCA-upregulation is suppressed by exogenous BNP.

Methods And Results: Here we tested the hypothesis that afterload and neurohumoral activation would counterregulate preload-dependent SERCA upregulation through BNP, which finally results in decreased SERCA levels.

Alpha1-adrenergic stress induces downregulation of Na+/Ca2+ exchanger in myocardial preparations from rabbits at physiological preload.

Alpha1-adrenergic stimulation and mechanical load are considered crucial for the expression of sarcolemmal Na+/Ca2+ exchanger (NCX1). However, the interaction between these processes is unknown. We investigated electrically stimulated (1 Hz, 1.

Relevance of brain natriuretic peptide in preload-dependent regulation of cardiac sarcoplasmic reticulum Ca2+ ATPase expression.

Background: In heart failure (HF), ventricular myocardium expresses brain natriuretic peptide (BNP). Despite the association of elevated serum levels with poor prognosis, BNP release is considered beneficial because of its antihypertrophic, vasodilating, and diuretic properties. However, there is evidence that BNP-mediated signaling may adversely influence cardiac remodeling, with further impairment of calcium homeostasis.

Mechanical load-dependent regulation of gene expression in monocrotaline-induced right ventricular hypertrophy in the rat.

Rats treated with monocrotaline (MCT) develop pulmonary hypertension. Their right ventricles (RVs) exhibit severe pressure overload-induced hypertrophy, whereas the left ventricles (LVs) are normally loaded. In contrast, enhanced neuroendocrine stimulation during the transition to heart failure affects both ventricles.