Cardiac secretion of adrenomedullin in human heart failure.

Abstract

Adrenomedullin (ADM) is a newly discovered endogenous vasorelaxing and natriuretic peptide. Recently, we have reported that plasma ADM is increased in severe congestive heart failure (CHF) in humans and that increased immunohistochemical staining is observed in the failing human ventricular myocardium. The present study was designed to test the hypothesis that the failing human ventricle secretes ADM and that circulating ADM progressively increases with the severity of clinical CHF. Plasma ADM was significantly increased in human CHF (39.8 Ϯ 3.6 pg/ml, P Ͻ 0.001 vs. normal) as compared with normal subjects (14.4 Ϯ 2.7 pg/ml). Plasma ADM was increased in mild CHF (NYHA class II, 30.1 Ϯ 3.4 pg/ml, P Ͻ 0.01 vs. normal), moderate CHF (NYHA class III, 31.5 Ϯ 3.0 pg/ml, P Ͻ 0.01 vs. normal), and severe CHF (NYHA class IV, 66.1 Ϯ 9.4 pg/ml, P Ͻ 0.001 vs. normal). In 13 patients with CHF in whom plasma samples were obtained from aorta (AO), coronary sinus (CS) and anterior interventricular vein (AIV), there was a significant step-up in plasma ADM between AO and AIV (50.6 Ϯ 9.3 pg/ml and 62.1 Ϯ 11.1 pg/ml, respectively, P Ͻ 0.01) and between AO and CS (50.6 Ϯ 9.3 pg/ml and 58.6 Ϯ 11.4 pg/ml, respectively, P Ͻ 0.05). The current study demonstrates that the failing human heart secretes ADM in human CHF suggesting contribution to the increase in plasma ADM, and indicates for the first time an additional endocrine system of cardiac origin which is activated in human CHF and may function in cardiorenal regulation. ( J. Clin. Invest. 1996. 97: 2370-2376.)

Plasma Adrenomedullin Levels in Patients with Non-Insulin Dependent Diabetes Mellitus: Close Relationships with Diabetic Complications.

“…The plasma adrenomedullin increased dependent on the severity of diabetic nephropathy and retinopathy. Adrenomedullin has been found in various tissues, including vascular smooth muscles, kidneys, cardiac tissues and lungs [2,3]. Previous studies reported that the plasma concentration of adrenomedullin increases in patients with hypertension, renal failure and congestive heart failure [4,5], though the major source of circulating adrenomedullin is unknown.…”

Circulating Adrenomedullin in Erythropoietin-Induced Hypertension.

“…Although the source of AM in the systemic circulation has not been conclusively identified (18,22,23), and although the conventional method of determining AM is not reliably accurate, most data would seem to indicate that there is an increase in circulating AM in patients with progressive renal disease (12,14,16). In our present study, the determination of AM was performed using a newly developed IRMA that provides a more accurate determination of the plasma concentration of biologically active circulating AM (mature AM).…”

Novel neuropeptides in the pathophysiology of heart failure: adrenomedullin and endothelin‐1

“…It is found in the vasculature (being synthesised and secreted from endothelial [20] and vascular smooth muscle cells [21]) and in both cardiac atria and ventricles [22]. Moreover ADM is secreted from the failing human heart and immunohistochemistry has revealed increased staining in failing ventricles [15,16]. ADM circulates in plasma at concentrations similar to ANP [23].…”

“…ADM circulates in plasma at concentrations similar to ANP [23]. Raised plasma concentrations in heart failure correlate with the symptomatic and haemodynamic severity of the syndrome [15][16][17][18][19]. In addition to being widespread in the cardiovascular system itself, ADM is found in closely allied tissues involved in regulation of vascular tone and fluid and electrolyte balance including the kidney, adrenal medulla and hypothalamo-pituitary axis [22].…”

“…Adrenomedullin ADM is a newly described 52 amino acid peptide the plasma concentrations of which are increased in patients with heart failure [15][16][17][18][19]. Although the precise role of ADM in the pathophysiology of heart failure is yet uncertain, its tissue distribution and properties suggest involvement in regulation of vascular tone and fluid and electrolyte balance.…”