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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ghrelin is a novel GH-releasing peptide that may also induce vasodilation and a positive energy balance through GH-independent mechanisms. However, the hemodynamic, renal, and hormonal effects of ghrelin in patients with chronic heart failure (CHF) remain unknown. Accordingly, 12 patients with CHF were given an iv infusion of human ghrelin (0.1 microg/kg.min) or placebo. Ghrelin significantly decreased mean arterial pressure (-9 mm Hg, P < 0.05) without a significant change in heart rate. Ghrelin significantly increased cardiac index (+25%, P < 0.05) and stroke volume index (+30%, P < 0.05), although it did not significantly alter mean pulmonary arterial pressure or pulmonary capillary wedge pressure. Infusion of ghrelin induced a marked increase in serum GH level (15-fold), associated with slight increases in circulating epinephrine, ACTH, cortisol, and PRL. Infusion of ghrelin did not significantly alter urine volume, urinary sodium excretion, or creatinine clearance. These hemodynamic, renal and hormonal parameters remained unchanged during placebo infusion. In summary, iv infusion of ghrelin, a potent GH-releasing peptide, had beneficial hemodynamic effects in patients with CHF in the absence of renal effects.
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PMID:Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. 1173 51

Ghrelin is a novel growth-hormone-releasing peptide isolated from the stomach that has been identified as an endogenous ligand for the growth-hormone secretagogue receptor. This peptide results in a positive energy balance by stimulating food intake and inducing adiposity through growth-hormone-independent mechanisms. In addition, ghrelin has several cardiovascular effects, as indicated by the presence of its receptor in blood vessels and ventricles of the heart. Infusion of ghrelin decreases systemic vascular resistance and increases cardiac output in patients with heart failure. Furthermore, repeated administration of ghrelin improves cardiac structure and function, and attenuates the development of cardiac cachexia in rats with heart failure. These results suggest that ghrelin has therapeutic potential in the treatment of severe chronic heart failure.
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PMID:Ghrelin improves left ventricular dysfunction and cardiac cachexia in heart failure. 1268 Dec 36

Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, which has been identified as an endogenous ligand for growth-hormone secretagogues receptor (GHS-R). This peptide also causes a positive energy balance by stimulating food intake and inducing adiposity through growth hormone-independent mechanisms. In addition, ghrelin has some cardiovascular effects, as indicated by the presence of its receptor in blood vessels and the cardiac ventricles. In vitro, ghrelin inhibits apoptosis of cardiomyocytes and endothelial cells. In humans, infusion of ghrelin decreases systemic vascular resistance and increases cardiac output in patients with heart failure. Repeated administration of ghrelin improves cardiac structure and function and attenuates the development of cardiac cachexia in rats with heart failure. These results suggest that ghrelin has cardiovascular effects and regulates energy metabolism through GH-dependent and -independent mechanisms. Thus, administration of ghrelin may be a new therapeutic strategy for the treatment of severe chronic heart failure (CHF).
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PMID:Ghrelin, a novel growth hormone-releasing peptide, in the treatment of chronic heart failure. 1283 93

Leptin and ghrelin are novel peptide hormones which are counter-regulatory in the central control of appetite. More recently, it has become clear that these hormones have a range of effects on the cardiovascular system. Leptin increases sympathetic activity, producing a pressor effect when acting on the central nervous system. However, leptin produces vasodilation by an endothelium-dependent mechanism peripherally. Ghrelin decreases sympathetic activity and has a depressor effect when acting on the central nervous system. Peripherally, ghrelin produces vasodilation by an endothelium-independent mechanism. Ghrelin improves left ventricular function and cardiac cachexia in heart failure. Leptin may contribute to cardiac cachexia, and to obesity-related cardiomyopathy by a variety of mechanisms. Leptin has pro-inflammatory, proliferative and calcification promoting effects in the vasculature. Ghrelin has recently been shown to be anti-inflammatory in the vasculature. Leptin may also produce a pro-thrombotic state through stimulation of platelet aggregation and inhibition of coagulation and fibrinolysis. The evidence for and against these effects as well as their pathophysiological significance in obesity hypertension, heart failure, atherosclerosis and thrombosis are discussed.
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PMID:The emerging roles of leptin and ghrelin in cardiovascular physiology and pathophysiology. 1585 36

Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, which has been identified as an endogenous ligand for GH secretagogue receptor. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. This peptide also stimulates food intake and induces adiposity through GH-independent mechanisms. In addition, ghrelin acts directly on the central nervous system to decrease sympathetic nerve activity. Thus, ghrelin plays important roles for maintaining GH release and energy homeostasis. Repeated administration of ghrelin improves body composition, muscle wasting, functional capacity, and sympathetic augmentation in cachectic patients with heart failure or chronic obstructive pulmonary disease. These results suggest that ghrelin has anti-cachectic effects through GH-dependent and independent mechanisms. Thus, administration of ghrelin may be a new therapeutic strategy for the treatment of cardiopulmonary-associated cachexia.
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PMID:Ghrelin, a novel growth hormone-releasing peptide, in the treatment of cardiopulmonary-associated cachexia. 1688 Jul 13

Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, which has been identified as an endogenous ligand for the GH secretagogues receptor. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated, not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. Considering the haemodynamic and anabolic effects of GH, ghrelin may have beneficial effects on cardiac function and energy metabolism in heart failure through GH-dependent mechanisms. On the other hand, ghrelin has some GH-independent actions: ghrelin stimulates food intake and induces adiposity. Interestingly, ghrelin acts directly on the CNS to decrease sympathetic nerve activity. It also inhibits apoptosis of cardiomyocytes and endothelial cells. An experimental study has shown that repeated administration of ghrelin improves cardiac structure and function, and attenuates the development of cardiac cachexia in chronic heart failure (CHF). These results suggest that ghrelin has cardiovascular effects and regulates energy metabolism through GH-dependent and -independent mechanisms. Thus, administration of ghrelin may be a new therapeutic strategy for the treatment of severe CHF.
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PMID:Therapeutic potential of ghrelin in the treatment of heart failure. 1659 62

Ghrelin infusion improves cardiac function in patients suffering from cardiac failure, and bolus administration of ghrelin increases cardiac output in healthy subjects. The cardiovascular effects of more continuous intravenous ghrelin exposure remain to be studied. We therefore studied the cardiovascular effects of a constant infusion of human ghrelin at a rate of 5 pmol/kg per minute for 180 min. Fifteen healthy, young (aged 23.2 +/- 0.5 yr), normal-weight (23.0 +/- 0.4 kg/m(2)) men volunteered in a randomized double-blind, placebo-controlled crossover study. With the subjects remaining fasting, peak myocardial systolic velocity S', tissue tracking TT, left ventricular ejection fraction EF, and endothelium-dependent flow-mediated vasodilatation were measured. Ghrelin infusion increased S' 9% (P = 0.002) and TT 10% (P < 0.001), whereas EF, resting blood flow velocity, and endothelium-dependent flow-mediated vasodilatation did not change (P = 0.13). This was associated with a peak in serum growth hormone after 60 min of infusion (37.77 +/- 5.27 ng/ml, P < 0.001), a doubling of free fatty acid levels (P = 0.001), and a 1.6-fold increase in cortisol levels (P < 0.05), whereas glucose and catecholamine levels were constant. In conclusion, supraphysiological levels of ghrelin stimulate left ventricular function in terms of S' and TT in healthy young normal-weight men without changing resting blood flow velocity and endothelium-dependent flow-mediated vasodilatation. The effects did not translate into detectable increments in EF.
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PMID:Cardiovascular effects of intravenous ghrelin infusion in healthy young men. 1787 22

Chronic exposure to hypoxia, a common adverse consequence of most pulmonary disorders, can lead to a sustained increase in pulmonary arterial pressure (PAP), right ventricular hypertrophy, and is, therefore, closely associated with heart failure and increased mortality. Ghrelin, originally identified as an endogenous GH secretagogue, has recently been shown to possess potent vasodilator properties, likely involving modulation of the vascular endothelium and its associated vasoactive peptides. In this study we hypothesized that ghrelin would impede the pathogenesis of pulmonary arterial hypertension during chronic hypoxia (CH). PAP was continuously measured using radiotelemetry, in conscious male Sprague Dawley rats, in normoxia and during 2-wk CH (10% O(2)). During this hypoxic period, rats received a daily sc injection of either saline or ghrelin (150 microg/kg). Subsequently, heart and lung samples were collected for morphological, histological, and molecular analyses. CH significantly elevated PAP in saline-treated rats, increased wall thickness of peripheral pulmonary arteries, and, consequently, induced right ventricular hypertrophy. In these rats, CH also led to the overexpression of endothelial nitric oxide synthase mRNA and protein, as well as endothelin-1 mRNA within the lung. Exogenous ghrelin administration attenuated the CH-induced overexpression of endothelial nitric oxide synthase mRNA and protein, as well as endothelin-1 mRNA. Consequently, ghrelin significantly attenuated the development of pulmonary arterial hypertension, pulmonary vascular remodeling, and right ventricular hypertrophy. These results demonstrate the therapeutic benefits of ghrelin for impeding the pathogenesis of pulmonary hypertension and right ventricular hypertrophy, particularly in subjects prone to CH (e.g. pulmonary disorders).
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PMID:Exogenous ghrelin attenuates the progression of chronic hypoxia-induced pulmonary hypertension in conscious rats. 1791 33

Ghrelin, mainly secreted from gastric mucosa, is the endogenous ligand for the growth hormone secretagogue receptor and induces a potent release of growth hormone. Ghrelin is widely expressed in different tissues and therefore has both endocrine and paracrine/autocrine effects. In this chapter, we summarize: (1) structure and distribution of ghrelin and its receptors; (2) myocardial effects of ghrelin, describing its acute and chronic actions on cardiac function; (3) ghrelin effects on smooth muscle, namely vascular smooth muscle, intraocular and gastrointestinal smooth muscle; and (4) skeletal actions of ghrelin. Ghrelin has a potent vasodilator effect, thereby reducing cardiac afterload and increasing cardiac output. In models of heart failure and myocardial ischemia, ghrelin administration has beneficial effects. At smooth muscle, ghrelin modulates vascular tone, increases gut transit, and relaxes iris muscles. In the skeletal muscle, ghrelin regulates resting membrane potential. In conclusion, there are increasing evidences that ghrelin is a peptide with paracrine actions that can modulate cardiac, smooth, and skeletal muscle functions.
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PMID:Cardiac, skeletal, and smooth muscle regulation by ghrelin. 1798 58

We had reported that increased levels of endogenous ghrelin during the progression of doxorubicin-induced cardiomyopathy and heart failure might provide a compensatory self-protective effect. We investigated which pathway(s) produced these protective effects in vitro. Primary cultured cardiomyocytes were induced with doxorubicin in the presence or absence of ghrelin or a tumor necrosis factor-alpha (TNF-alpha) antagonist (etanercept). Ghrelin up-regulated TNF-alpha in a time- and dose-dependent manner. It significantly reduced cell apoptosis and markers of oxidative stress, such as malondialdehyde (MDA) content and lactate dehydrogenase (LDH) activity; it also increased anti-oxidative enzyme activity such as superoxide dismutase (MnSOD) and catalase (CAT), retained mitochondrial membrane potential and energy metabolism compared with doxorubicin alone. Moreover, ghrelin increased mitochondrial anti-apoptosis related gene protein expression such as bcl-2 and MnSOD, reduced cytoplasmic cytochrome C (Cyt C) release and strengthened the activation of NF-kappaB. All these effects were abrogated by etanercept. This suggests ghrelin affects the TNF-alpha/NF-kappaB activation pathways, up-regulating TNF-alpha, to produce anti-oxidative and anti-apoptotic effects that protected cardiomyocytes from doxorubicin-induced cytotoxicity.
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PMID:Ghrelin prevents doxorubicin-induced cardiotoxicity through TNF-alpha/NF-kappaB pathways and mitochondrial protective mechanisms. 1840 Mar 55


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