Atrial natriuretic peptide increases adrenomedullin in the circulation of healthy humans

Vesely, David L.; Blankenship, Mary; Douglass, Margaret A.; McCormick, Michael; Rodriguez-Paz, G; Schocken, Douglas D.

doi:10.1016/0024-3205(96)00290-1

Cited by 35 publications

(15 citation statements)

References 24 publications

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“…Indeed, in support of this, it was recently reported that ANP infusion increases plasma ADM concentration in healthy humans, although this finding requires confirmation. 19,20 Even if NEP were involved in ADM degradation in the study of Lisy et al, 15 their findings could reflect a species difference or, more likely, a tissue difference. The kidney is particularly rich in NEP, and this may explain the discrepancy between the present findings and those of Lisy et al 15 However, the only other study we can find in the literature on the possible role of NEP in the metabolism of ADM suggests that even in the kidney, NEP may not metabolize ADM. 21 Lewis et al 21 CABG indicates coronary artery bypass graft surgery; NYHA, New York Heart Association; MI, myocardial infarction; CHD, coronary heart disease; HMG CoA, 3-hydroxy-3-methylglutaryl coenzyme A.…”

Section: Discussionmentioning

confidence: 63%

Effect of Neutral Endopeptidase Inhibition on the Actions of Adrenomedullin and Endothelin-1 in Resistance Arteries From Patients With Chronic Heart Failure

Petrie

Hillier²,

Johnston³

et al. 2001

Hypertension

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Abstract-Adrenomedullin and endothelin are novel peptides that are produced in the blood vessel wall and have contrasting biologic actions. Both may play a pathophysiological role in atherosclerosis and chronic heart failure. It has also been suggested that both peptides may be metabolized by neutral endopeptidase and that pharmacological manipulation of this enzyme may be of therapeutic interest. We investigated the effect of thiorphan, a neutral endopeptidase inhibitor, on the vasodilator response to adrenomedullin and the vasoconstrictor response to endothelin in small resistance arteries taken from patients with heart failure caused by coronary heart disease. Small resistance arteries were dissected from gluteal biopsy samples and studied with wire myography. Thiorphan did not affect the vasodilator response to adrenomedullin in arteries preconstricted with norepinephrine. Maximal responses were 66% (SD 11%) and 72% (8%) in the absence and presence of thiorphan, respectively (nϭ8). The vasoconstrictor response to endothelin was also unaffected. The maximum vasoconstrictor responses in the absence and presence of thiorphan were 152% (11%) and 132% (12%), respectively (nϭ8). The values of corresponding Ϫlog concentrations of agonist required to effect a 50% response (pD 2 ) were 8.52 (0.11) and 8.64 (0.15), respectively. We showed that the inhibition of neutral endopeptidase does not augment the vasodilator and vasoconstrictor activities of adrenomedullin and endothelin, respectively, in small resistance arteries from patients with chronic heart failure. This suggests that neutral endopeptidase inhibition, as a therapeutic strategy, will enhance neither the potentially desirable vascular actions of adrenomedullin nor the potentially unfavorable vascular effects of endothelin-1 in human cardiovascular disease states.

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Section: Discussionmentioning

confidence: 63%

Effect of Neutral Endopeptidase Inhibition on the Actions of Adrenomedullin and Endothelin-1 in Resistance Arteries From Patients With Chronic Heart Failure

Petrie

Hillier²,

Johnston³

et al. 2001

Hypertension

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“…Hormonal factors such as adrenocorticosteroids, thyroid hormones, and atrial natriuretic factor (ANF) stimulate ADM release (Minamino et al 1995;Vesely et al 1996). Of these known hormones, we can eliminate ANF as a significant factor, since ANF levels are not elevated in late pregnancy (Zhang et al 1995).…”

Section: (B) Effect Of Steroid Hormones On Plasma Adm Levelsmentioning

confidence: 98%

Effect of pregnancy and steroid hormones on plasma adrenomedullin levels in the rat

Jerat¹,

Kaufman²

1998

Can. J. Physiol. Pharmacol.

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Pregnancy is characterized by volume expansion and vasodilation. We investigated whether the hypotensive peptide adrenomedullin (ADM) might be a significant factor in the cardiovascular adaptation to pregnancy. Rats were prepared with indwelling cannulae. Plasma ADM levels were measured by RIA before mating, at 7, 14, and 21 days of pregnancy, and at 7 days postpartum. We also investigated the effects on plasma ADM levels of administering estrogen, progesterone, and the metabolite of progesterone 3 alpha-OH-5 alpha-pregnan-20-one (3 alpha-OH-DHP); this last steroid has been implicated in altering reflex control of blood pressure and volume during pregnancy. Plasma ADM levels increased progressively during pregnancy from 123 +/- 27 pg/mL in virgin animals to 404 +/- 50 pg/mL at 21 days of pregnancy. The levels returned to pre-pregnancy values postpartum. 3 alpha-OH-DHP caused a significant rise in plasma ADM levels, whereas neither estrogen nor progesterone had any effect. We suggest that ADM may be an important contributing factor to the vasodilation associated with normal pregnancy. Active metabolites of progesterone, rather than progesterone itself, may be at least partially responsible for stimulating the release of ADM.

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“…10,11 Preliminary data suggest that there may be interactions between ADM, produced primarily in the peripheral circulation, and the cardiac natriuretic peptides produced in the heart. 12,13 Currently, however, there is no information regarding the effects of infused ADM in patients with heart failure and no data directly comparing the biological actions of ADM and BNP. Furthermore, the effects of coadministration of ADM and BNP in humans are unknown.…”

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confidence: 99%

Bioactivity and Interactions of Adrenomedullin and Brain Natriuretic Peptide in Patients With Heart Failure

et al. 1999

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Abstract-Plasma concentrations of the recently discovered hormones adrenomedullin (ADM), from vascular tissue, and brain natriuretic peptide (BNP), secreted by myocardium, are elevated in patients with heart failure. We tested the hypotheses that short-term increments in circulating levels of these hormones, within the pathophysiological range, would have biological effects and that the 2 hormone systems interact. Eight patients with heart failure (left ventricular ejection fractions Ͻ35%) received 4-hour infusions of BNP (3.0 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) alone, ADM (2.7 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 and 5.4 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 for 2 hours each) alone, ADM and BNP combined, and placebo. BNP and ADM infusions raised plasma levels of the respective peptide within the pathophysiological range. Arterial blood pressure fell (PϽ0.05) with all peptide infusions, but cardiac output was unchanged. Heart rate increased with ADM and combined infusions (PϽ0.01). Sodium excretion rose (PϽ0.05), and creatinine clearance was sustained during both BNP and combined infusions. Urine volume increased in response to BNP alone (Pϭ0.02). Despite a Ͼ2-fold increase in plasma renin with both ADM and combined infusions (PϽ0.05), plasma aldosterone remained lower than time-matched placebo levels. Plasma noradrenaline was increased by combined, BNP, and higher dose ADM infusions (PϽ0.05). ADM suppressed plasma cGMP (PϽ0.05) and inhibited the plasma cGMP response to BNP (PϽ0.05). The vascular hormones ADM and BNP, produced by myocardium, at plasma concentrations within the pathophysiological range have hemodynamic, renal, and hormonal effects and measurable interactions in patients with heart failure. (Hypertension. 1999;34:70-75.) Key Words: heart failure Ⅲ adrenomedullin Ⅲ natriuretic peptides Ⅲ arterial pressure N eurohormonal activation plays a crucial role in the pathophysiology of heart failure. 1 Adrenomedullin (ADM), discovered in 1993, 2 and brain natriuretic peptide (BNP) are peptides with vasodilator, natriuretic, and aldosterone-inhibitory actions. 3-5 Plasma levels of both peptides are increased in proportion to the degree of hemodynamic compromise. 6,7 BNP is secreted predominantly from the left ventricle in response to increases in wall stress, whereas production of ADM from cultured endothelial and vascular smooth muscle cells suggests that blood vessels may be a major source of circulating ADM. 8,9 It is likely that ADM functions in an autocrine or paracrine fashion in addition to any role it may have as a circulating hormone because tissues with ADM receptors are also those with ADM synthetic capability. 10,11 Preliminary data suggest that there may be interactions between ADM, produced primarily in the peripheral circulation, and the cardiac natriuretic peptides produced in the heart. 12,13 Currently, however, there is no information regarding the effects of infused ADM in patients with heart failure and no data directly comparing the biological actions of ADM and BNP. Furthermore, the effects of coadministration of ADM and BNP in ...

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Atrial natriuretic peptide increases adrenomedullin in the circulation of healthy humans

Cited by 35 publications

References 24 publications

Effect of Neutral Endopeptidase Inhibition on the Actions of Adrenomedullin and Endothelin-1 in Resistance Arteries From Patients With Chronic Heart Failure

Effect of Neutral Endopeptidase Inhibition on the Actions of Adrenomedullin and Endothelin-1 in Resistance Arteries From Patients With Chronic Heart Failure

Effect of pregnancy and steroid hormones on plasma adrenomedullin levels in the rat

Bioactivity and Interactions of Adrenomedullin and Brain Natriuretic Peptide in Patients With Heart Failure

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