Peripheral distribution and gene expression of adrenomedullin in the rat: possible source of blood adrenomedullin

Hwang, Isabel S.S.; Tang, Florence

doi:10.1054/npep.1999.0783

Cited by 44 publications

(34 citation statements)

References 19 publications

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“…Rat AM mRNA-expression studies suggest that there are species differences as well as differences in each model of cardiomyopathy. In addition, there appears to be a great variability in the correlation of cardiac AM protein and mRNA expression; e.g., in healthy male Wistar rat myocardium (6,29), AM tissue concentrations are 10-20 times higher in atrial myocardium than in ventricular myocardium, whereas mRNA expression appears to be increased by only 20%. The latter data are similar to our results from sham SHR.…”

Section: Discussionmentioning

confidence: 99%

Gene expression of adrenomedullin in failing myocardium: comparison to atrial natriuretic peptide

Bäumer¹,

Schumann²,

Cremers

et al. 2002

Journal of Applied Physiology

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2001.-The expression of adrenomedullin (AM) and atrial natriuretic factor (ANF) were investigated in the myocardium of a rat model of chronic ischemic heart failure (CHF) compared with sham-operated controls. In addition, human myocardium of patients with end-stage heart failure due to idiopathic dilated cardiomyopathy compared with myocardium of normal subjects (NF) was studied. In CHF, similar AM levels but increased ANF expression were observed in left ventricular myocardium, as assessed by semiquantitative PCR. Functional experiments with freshly excised papillary muscles showed no influence of AM on myocardial contractility. In NF human myocardium, the expression of AM mRNA was threefold higher in atrial compared with ventricular tissue. In analogy, ANF mRNA was increased by ϳ15-fold in atrial tissue. In dilated cardiomyopathy, the expression of AM was significantly increased in right and left ventricles compared with NF. In parallel, ventricular ANF expression was enhanced. heart failure; adrenomedullin; myocardial inotropy; atrial natriuretic factor; gene expression PREVIOUS REPORTS DEMONSTRATED that plasma levels of adrenomedullin (AM) are increased in patients with heart failure (12,16,20,23) and ventricular hypertrophy (4). Recent reports suggest that, other than its effects on vascular tone and natriuresis, physiological concentrations of AM may influence myocardial inotropy (7,27). Several groups demonstrated the importance of AM as an auto-and paracrine mechanism for modulation of cellular growth and development (3,8,21,28). As a strong nitric oxide-liberating peptide in the vascular system, systemic and coronary circulation is regulated by AM (5). These results indicate that AM might be involved in the pathophysiology of cardiac hypertrophy and heart failure. Where circulating AM originates from is still debated, but recent data suggest that cardiac AM expression contributes to elevated serum levels in patients with heart failure (9, 29). Under physiological conditions, atrial levels of AM are among tissues of highest expression in the body. High levels of atrial expression (21), its colocalization with the expression of atrial natriuretic peptide, and almost identical physiological actions of AM and atrial natriuretic factor (ANF) (21) led to the hypothesis that, in addition to its local auto-and paracrine effects, AM may also act as a humoral factor of cardiorenal homeostasis.In the present study, gene expression of AM in atrial and ventricular myocardium at two stages of the development of chonic heart failure in spontaneously hypertensive rats (SHR) and idiopathic human heart failure were investigated. Therefore, hearts of SHR with chronic ligation of the left coronary artery as a well characterized model of congestive heart failure (CHF) and myocardium of explanted human hearts with end-stage heart failure due to idiopathic dilated cardiomyopathy (DCM) were investigated. The expression levels of AM were compared with the expression of ANF, a sensitive marker of cardiac hypertrophy and failure....

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Section: Discussionmentioning

confidence: 99%

Gene expression of adrenomedullin in failing myocardium: comparison to atrial natriuretic peptide

Bäumer¹,

Schumann²,

Cremers

et al. 2002

Journal of Applied Physiology

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“…These observations strongly support our in vitro findings. Previously, no significant difference was observed among ir-AM levels in the venous blood from the kidney, lung, adrenal gland and systemic arterial blood of rats (53). However, a significantly lower concentration in the left ventricle and aorta compared to venous side of circulation was reported in some studies and it was also proved that the lung is the major site of AM clearance in humans (54,55).…”

Section: Am Production In the Cerebral Microcirculationmentioning

confidence: 94%

Adrenomedullin, an Autocrine Mediator of Blood-Brain Barrier Function

et al. 2003

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“…An aliquot of 2 ml plasma was acidifi ed with 1 % TFA and purifi ed by Sep-column (Peninsula, Belmont, CA, U.S.A.) as reported previously [18] . The plasma extract was further purifi ed by a nano-spin column (Gelman, Ann Arbor, MI, U.S.A., molecular cut-off 10 kD) to remove the large molecular weight AM precursor [5] .…”

Section: Extraction Of Am From Tissues and Plasmamentioning

confidence: 99%

“…It is widely distributed and has many physiological functions [2] . AM gene expression and peptides have been found in the heart and blood vessels of humans [3,4] and in rats [5] . AM is secreted by the endothelial cells [6] and smooth muscle cells [7] of the vasculature.…”

Section: Introductionmentioning

confidence: 99%

Adrenomedullin Gene Expression and Peptide Levels in the Heart and Blood Vessels of Streptozotocin-diabetic Rats

Tang

Hwang²,

Wong³

et al. 2007

Horm Metab Res

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The aim of the present study was to assess the changes in gene expression and peptide adrenomedullin (AM) levels in cardiovascular and other tissues in the streptozotocin-diabetic rats. For this purpose, diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/Kg body weight). Half of the diabetic rats were subcutaneously injected with insulin in the afternoon (4 units/day) one week after STZ injection until the day before killing. Control rats received only saline injection. AM mRNA was determined in cardiovascular and other tissues of streptozotocin-diabetic rats using solution-hybridization-RNase protection assay. Circulating AM and peptide AM in cardiovascular and other tissues were estimated using a specific radioimmunoassay. There were increases in preproAM mRNA levels in the left and right ventricles and in the thoracic aorta in both the 2-week and 4-week diabetic rats, but not in the two atria, the mesenteric artery and the lung. In the 2-week diabetic rats, there were decreases in AM contents in the two atria and the lung but an increase in the thoracic aorta. In the 4-week diabetic rats, there were bigger decreases in the atria and also a decrease in the left ventricle. The plasma AM levels were not changed but there was an increase in the excretion of AM in the urine. Our results suggest a possible increase in AM release in the heart and the thoracic aorta in the 2-week and 4-week diabetic rats.

show abstract

Peripheral distribution and gene expression of adrenomedullin in the rat: possible source of blood adrenomedullin

Cited by 44 publications

References 19 publications

Gene expression of adrenomedullin in failing myocardium: comparison to atrial natriuretic peptide

Gene expression of adrenomedullin in failing myocardium: comparison to atrial natriuretic peptide

Adrenomedullin, an Autocrine Mediator of Blood-Brain Barrier Function

Adrenomedullin Gene Expression and Peptide Levels in the Heart and Blood Vessels of Streptozotocin-diabetic Rats

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