M T Rademaker

..The goal of this study was to determine the bioactivity of urocortin (Ucn) in experimental heart failure (HF)...

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..Manipulation of the AM system holds promise as a therapeutic strategy in cardiac disease...

..To investigate the subacute effects of a sustained intravenous infusion of urocortin-I (Ucn-I) in experimental heart failure (HF)...

..Urocortin 2 (Ucn2) has potent cardiovascular actions and may participate in the pathophysiology of heart failure (HF). The integrated hemodynamic, endocrine, and renal effects of Ucn2 are unknown...

..These findings support the concept of adrenomedullin as a protective hormone during hemodynamic compromise with therapeutic potential in heart failure...

..To investigate the haemodynamic, hormonal, and renal effects of peripheral urocortin 3 (Ucn3) administration for the first time in either normal health or heart failure (HF)...

..Despite the greater falls in blood pressure (and presumably renal perfusion pressure), renal function was maintained at a level similar to that observed with captopril alone...

..These results indicate that dual treatment with these two agents is beneficial...

..In conclusion, cotreatment with adrenomedullin and an endopeptidase inhibitor has beneficial hemodynamic and renal effects in heart failure beyond those of either agent separately...

..To investigate the role of the endogenous urocortin peptides in heart failure (HF) through blockade of the corticotropin-releasing factor receptor 2 (CRF-R2)...

..These data strongly support a use for Ucn1 as a therapeutic option early in the course of the disease...

..The effects of AM2 in heart failure have not been investigated previously...

..Because any prospective new treatment is likely to be used in conjunction with standard diuretic therapy, it is necessary to investigate the combined effects of these agents...

..This is a reproducible model that reflects the clinical condition and should prove suitable for investigating the pathophysiology of, and experimental therapies in, early left ventricular dysfunction...

..The favourable biological properties of the natriuretic peptides have also led to their use as therapeutic agents...

..001). In conclusion, ADM induces a different spectrum of hemodynamic, renal, and endocrine actions to NP. These results clarify mechanisms by which ADM might contribute to volume and pressure homeostasis...

..In conclusion, adrenomedullin within the central nervous system may have at least two roles: modulation of the hypothalamo-pituitary-adrenal axis and protection against fluid overload...

..These results provide further evidence that ADM plays a physiological role in volume and pressure homeostasis...

..039) and adrenocorticotrophic hormone (P=0.012) were decreased by ADM. In conclusion, ADM-induced augmentation of the RAS and HPA responses to hypotensive haemorrhage is abolished in the pregnant state...

..The data suggest a possible role for adrenomedullin in cardiovascular homeostasis in part through antagonism of the vasopressor action of angiotensin II...

..This is the first report of ANP expression and synthesis by cardiac fibroblasts invading the fibrotic scar, suggesting that ANP may be involved in regulating fibroblast proliferation during reparative fibrosis...

..Acute changes in biochemical markers, haemodynamics, neurohormones and LV function confirm that these are excellent models of open- and closed-artery myocardial infarction leading to asymptomatic LV dysfunction...

..In contrast to AM, AM2 had no restraining influence on the aldosterone response to Ang II. The data suggest a possible role for AM2 in cardiovascular homeostasis in part through antagonism of the vasopressor action of Ang II...

..Urocortin 1 (Ucn1) and the sympathetic nervous system both participate in cardiac and circulatory regulation, but little is known about their possible interactions...

..We sought to examine the effects of urocortin (UCN) 2 infusion on hemodynamic status, cardiovascular hormones, and renal function in healthy humans...

..The threshold for the action of Ucn1 on the natriuretic peptides and endothelin-1 appears to be below that of other actions of Ucn1...

..Clearly, further study is essential to confirm whether manipulation of this new family of peptides (especially Ucn II and Ucn III) offers benefit to the syndrome of heart failure with potential clinical applications in humans...

..Apelin also increases circulating levels of a number of vasoactive hormones. Taken together, these results suggest a potential role for apelin in pressure/volume homeostasis...

..This is the first report identifying sources of circulating Ucn-1...

..The latter effect might contribute to the anorexic action of Ucn-1...

..Thus, these results clearly point to a role for AM in pressure and volume homeostasis acting, at least in part, by interaction with the renin-angiotensin-aldosterone system (RAAS)...

..ANP and ghrelin were unchanged, and no haemodynamic or renal effects were seen. In conclusion, a brief intravenous infusion of 50 microg of Ucn 1 stimulates corticotropin and cortisol in male volunteers with stable HF...

..This study provides evidence that natriuretic peptides play a pivotal role in preserving volume/electrolyte balance in the early stages of post-MI cardiac dysfunction...

..Circulating levels of CNP and NT-CNP were raised in heart failure but to a much lesser degree than ANP and BNP. There was no evidence of net extraction of CNP or NT-CNP across any tissue bed...

..Significant arteriovenous gradients were observed across the heart (36%), liver (40%) and kidney (44%). This is the first report to identify the heart, liver and kidney as sources of UII in the circulation...

..Thus, AM-2 may be another important regulator of volume and pressure homeostasis and may play a role in the pathophysiology of heart disease...

..These findings suggest an important role for UCN2 in cardiovascular homeostasis and warrant further investigation for potential therapeutic applications in acute myocardial injury and heart disease...

..To document the haemodynamic, neurohormonal, and renal responses to Urocortin 2 (UCN2) infused in human heart failure (HF)...

..An improved understanding of the role of adrenomedullin in heart failure might lead to the development of therapeutic agents acting through adrenomedullin receptors...

..Moreover, whether the cultured cardiac fibroblasts are from infarct tissue is a major determinant of NPR expression levels and cytokine responses, even after four to five passages...