Most vertebrates increase cardiac output during activity by elevating heart rate with relatively stable stroke volume. However, several studies have demonstrated 'intrinsic autoregulation' of cardiac output where artificially increased heart rate is associated with decreased stroke volume, leaving cardiac output unchanged. We explored the capacity of noradrenaline to overcome autoregulation in ...

KEY POINTS Omecamtiv mecarbil and blebbistatin perturb the regulatory state of the thick filament in heart muscle. Omecamtiv mecarbil increases contractility at low levels of activation by stabilizing the ON state of the thick filament. Omecamtiv mecarbil decreases contractility at high levels of activation by disrupting the acto-myosin ATPase cycle. Blebbistatin reduces contractility by stabil...

BACKGROUND The major source of nitric oxide (NO) in the heart is the constitutive form of NO synthases (eNOS, NOS III) that is expressed in vascular endothelium and cardiac myocytes. NO mediates endothelium-dependent vasodilation and may modulate cardiac function. We examined the role of NO in hearts from transgenic (TG) mice overexpressing eNOS exclusively in cardiac myocytes. METHODS AND RE...

Significance We custom synthesize a fluorescent ligand and use highly sensitive microscopy methods to show that receptors may be targeted distinct sites of cell. provide microscopic images the localization ? 1 ?adrenergic (? -ARs) 2 ?ARs), main drivers contractility heart, in heart muscle cells. ?ARs are exclusively specific structures these cells, T-tubules, while -ARs found at entire cell sur...

Chronic administration of aldosterone promotes myocardial fibrosis in rats. The Randomized Aldactone Evaluation Study reported that the aldosterone antagonist spironolactone improved outcome in patients with congestive heart failure, suggesting a deleterious effect of aldosterone in the heart. Aldosterone has been shown to have rapid nongenomic effects in different tissues including the heart. ...

RATIONALE Protein kinase Cα (PKCα) activity and protein level are induced during cardiac disease where it controls myocardial contractility and propensity to heart failure in mice and rats. For example, mice lacking the gene for PKCα have enhanced cardiac contractility and reduced susceptibility to heart failure after long-term pressure overload or after myocardial infarction injury. Pharmacolo...

Rationale: Protein kinase C (PKC ) activity and protein level are induced during cardiac disease where it controls myocardial contractility and propensity to heart failure in mice and rats. For example, mice lacking the gene for PKC have enhanced cardiac contractility and reduced susceptibility to heart failure after long-term pressure overload or after myocardial infarction injury. Pharmacolog...

Heart failure is one of the most prevalent diseases in industrialized countries. Although the prognosis of patients with heart failure is still poor, in recent decades new therapies have been investigated in order to improve quality of life and survival. However, up to 30% of the patients with advanced heart failure present disturbances in intraventricular conduction, and this produces asynchro...