Background-An activated endothelin (ET) system may be of pathophysiological relevance in human heart failure. We characterized the functional effects of ET-1, ET receptors, and ET-1 peptide concentration in left ventricular myocardium from 10 nonfailing hearts (NF) and 27 hearts in end-stage failure due to idiopathic dilative cardiomyopathy (DCM).

Cardiac-specific overexpression of murine cardiac calsequestrin results in depressed cardiac contractile parameters, low Ca 2؉ -induced Ca 2؉ release from sarcoplasmic reticulum (SR) and cardiac hypertrophy in transgenic mice. To test the hypothesis that inhibition of phospholamban activity may rescue some of these phenotypic alterations, the calsequestrin overexpressing mice were cross-bred with phospholamban-knockout mice. Phospholamban ablation in calsequestrin overexpressing mice led to reversal of the depressed cardiac contractile parameters in Langendorff-perfused hearts or in vivo. This was associated with increases of SR Ca 2؉ storage, assessed by caffeine-induced Na ؉ -Ca 2؉ exchanger currents. The inactivation time of the L-type Ca 2؉ current (I Ca ), which has an inverse correlation with Ca 2؉ -induced SR Ca 2؉ release, and the relation between the peak current density and half-inactivation time were also normalized, indicating a restoration in the ability of I Ca to trigger SR Ca 2؉ release. The prolonged action potentials in calsequestrin overexpressing cardiomyocytes also reversed to normal upon phospholamban ablation. Furthermore, ablation of phospholamban restored the expression levels of atrial natriuretic factor and ␣-skeletal actin mRNA as well as ventricular myocyte size. These results indicate that attenuation of phospholamban function may prevent or overcome functional and remodeling defects in hypertrophied hearts.Hypertrophy of ventricular myocardium is postulated to be an adaptive response to relative increases in external workload, induced by endocrine, paracrine, autocrine, and mechanical factors or decreased myocardial contractility (1). The increase in heart mass has been implicated to normalize cardiac function by decreasing wall stress. However, a sustained imbalance between workload and muscle contractility may lead to progressive thinning of the left ventricular wall and chamber dilation associated with decompensated hypertrophy and heart failure (2, 3). Studies in human and animal models have shown that cardiac hypertrophy is associated with impaired sarcoplasmic reticulum (SR) 1 Ca 2ϩ modulation, leading to aberrant cardiac contraction and relaxation (4 -8). Although several Ca 2ϩ -related signaling molecules, such as calcineurin, Ca 2ϩ -calmodulin kinase, and Ca 2ϩ

Pro-ANP plasma levels are independently and inversely related to anxiety. Even in severe CHF with severely compromised quality of life, anxiety tends to decrease with high pro-ANP levels. This might be part of a negative feedback loop limiting psychological distress and its adverse autonomic consequences in severe heart failure.

These data demonstrate that the KAI1 mRNA expression and the KAI1 protein level increase in an earlier tumor stage of colorectal cancer, decrease in advanced stages, and are lost in metastases. The loss of KAI1 might favor the ability of colorectal cancer cells to metastasize.

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A strong immunoreactivity for ECE-1 can be found in the blood vessels of the retina, optic nerve and choroid. Therefore, it should be possible to treat ET-1-induced vaso-constriction in the eye using ECE-1 inhibitors, especially in diseases like hypertensive vasculopathy, vasospasm, vaso-occlusions or low tension glaucoma.