Hemodynamic, Renal, and Hormonal Effects of Adrenomedullin Infusion in Patients With Congestive Heart Failure

Nagaya, Noritoshi; Satoh, Tsuyoshi; Nishikimi, Toshio; Uematsu, Masaaki; Furuichi, Shinichi; Sakamaki, Fumio; Oya, Hideo; Kyotani, Shingo; Nakanishi, Norifumi; Goto, Yoichi; Masuda, Yoshiaki; Miyatake, Kunio; Kangawa, Kenji

doi:10.1161/01.cir.101.5.498

Cited by 243 publications

(197 citation statements)

References 22 publications

Supporting

Mentioning

179

Contrasting

Unclassified

Order By: Relevance

“…15 Previous human experiments have produced varied results on the effects of intravenous infusion of AM on aldosterone release. [8][9][10][11][12] Our study showed that suppression of aldosterone release by AM in the control group was significant but quite limited (Figure 3). A hypotensive reaction due to AM infusion was observed over a wide dosage range, but the suppressive effect of AM on aldosterone release was time and dose dependent, suggesting that there may be relatively high thresholds for suppression.…”

Section: Effects Of Adrenomedullin In Primary Aldosteronismmentioning

confidence: 73%

“…AM administration stimulates renin release. [8][9][10][11][12] On the other hand, AM can partially, but not completely, suppress increases in aldosterone induced by angiotensin II in humans. 17 In PA patients, renin activity is extremely suppressed, suggesting that AM could mediate essential aldosterone suppression.…”

Section: Effects Of Adrenomedullin In Primary Aldosteronismmentioning

confidence: 99%

“…AM did not affect ANP or BNP levels in normal subjects or in patients with hypertension or heart failure. 9,10,12 The ANPstimulating effect in PA patients is interesting, although the mechanism is unclear. ANP inhibits aldosterone secretion and is considered to be a key factor in aldosterone escape (or aldosterone breakthrough).…”

Section: Effects Of Adrenomedullin In Primary Aldosteronismmentioning

confidence: 99%

“…26,27 In addition to the decrease in cardiac afterload induced by vasodilation, cardiac output was markedly increased by AM administration. [9][10][11][12] The cumulative increase in BNP may reflect cardiac overload induced by prolonged infusion of AM. Although none of the participants experienced adverse events, cardiac overload must be carefully avoided during longer term application of AM.…”

Section: Effects Of Adrenomedullin In Primary Aldosteronismmentioning

confidence: 99%

“…AM suppressed aldosterone levels in secondary hyperaldosteronism, such as experimental heart failure in sheep 8 or congestive heart failure in patients. 12 These data suggest that AM may be a functional antagonist of aldosterone release, but further evidence is required. We investigated the effects of AM in patients with primary aldosteronism (PA) to confirm the antagonistic effect of AM against aldosterone.…”

Section: Introductionmentioning

confidence: 96%

See 4 more Smart Citations

Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in patients with primary aldosteronism

2010

View full text Add to dashboard Cite

Adrenomedullin (AM) is located in the zona glomerulosa of the adrenal cortex and is considered to suppress aldosterone release. To determine the effect of AM in primary aldosteronism (PA), we infused AM (2.5 pmol kg À1 min À1 ) for 27 h, followed by a 15-h recovery period, in a control group (essential hypertensives with plasma aldosterone levels p100 pg ml À1 , n¼7) and in a PA group (n¼5). The control group was also infused with vehicle. Hemodynamic, hormonal, oxidative and inflammatory responses were studied. AM infusion caused similar and steady decreases in blood pressure and several markers for arteriosclerosis (for example, pulse wave velocity) in both groups. Interestingly, AM infusion suppressed aldosterone release to values within the normal range in the PA group (300.0 ± 58.4 to 111.6 ± 13.5 pg ml À1 , Po0.01). In the control group, aldosterone release suppression was significant but limited (81.7 ± 9.1 to 47.9 ± 9.9 pg ml À1 , Po0.01). The adrenocorticotropic hormone-cortisol system was not changed by AM infusion. Brain natriuretic peptide was cumulatively increased by prolonged AM infusion in both groups, probably because of cardiac overload. AM did not affect oxidative markers. In addition, a mild but significant increase in C-reactive protein (CRP) mediated by interleukin-6 was observed during AM infusion in every participant, without exception. This pathway might participate in CRP elevation in cardiovascular disease. In summary, AM seems to have an essential role in the suppression of aldosterone release in PA. AM may be an important modulator in PA, and intermediate-term Keywords: adrenomedullin; aldosterone; C-reactive protein; humans; primary aldosteronism INTRODUCTION Adrenomedullin (AM) is a potent hypotensive peptide found ubiquitously in tissues and organs, especially in cardiovascular tissues, the kidneys, lungs and endocrine glands. AM has multiple functions in a wide range of tissues and acts mainly as a vasodilatory and proliferation-inhibitory factor. 1 AM was initially identified in the adrenal medulla, but similar densities of AM were detected in the zona glomerulosa of the adrenal cortex, where AM suppresses aldosterone release. 2,3 In addition, expression of AM and its receptor was detected in Conn's adenoma cells, and AM exerted aldosterone antisecretagogue action and proliferative effects on cultured Conn's adenoma cells. 4 These findings suggest that endogenous AM may be an important modulator of aldosterone release in normal and pathogenic hyperaldosteronism. In addition, AM antagonized aldosterone-induced vascular or cardiac remodeling 5,6 and suppressed aldosterone-induced oxidative stress in a malignant hypertensive model. 7 The characteristics that define this compound, from its release to alterations in target organs, suggest that AM may be an endogenous anti-aldosterone factor, especially in the cardiovascular system.

show abstract

Section: Effects Of Adrenomedullin In Primary Aldosteronismmentioning

confidence: 73%

Section: Effects Of Adrenomedullin In Primary Aldosteronismmentioning

confidence: 99%

Section: Effects Of Adrenomedullin In Primary Aldosteronismmentioning

confidence: 99%

Section: Effects Of Adrenomedullin In Primary Aldosteronismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 3 more Smart Citations

Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in patients with primary aldosteronism

2010

View full text Add to dashboard Cite

show abstract

Endogenous Vasoactive Peptides

Webb

Ksander²

2010

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

The control of vasomotor tone regulates the overall cardiovascular system and its responses to physiological and pathophysiological stress. It provides differential blood flow to regional vascular beds under normal physiologic conditions, at times of normal stress, such as exercise, and during conditions of pathological stress, such as congestive heart failure. Although the vascular system regulates many of its functions at the site of the blood vessel itself, other factors that may control vascular tone include the autonomic nervous system, circulating hormones functioning in an endocrine role, and reflex metabolic control. Many newly discovered peptides were found to be widespread in autonomic and sensory neurons innervating the vasculature, and they possess potent vasoactive effects on many blood vessels. Vasoactive peptides have been shown to play an important role in many pathological situations, for example, asthma, arthritis, vascular headaches, hypertension, and other cardiovascular diseases. In this chapter, we will outline the evidence for the different actions of various vasoactive peptides, their interaction with other systems, the possible role they have in diseases, and the present and future therapeutic use of vasoactive peptide agonists and antagonists.

show abstract

Biomarkers of Cardiac Injury

McLean¹,

Huang²

2010

Biomarkers

View full text Add to dashboard Cite

Hemodynamic, Renal, and Hormonal Effects of Adrenomedullin Infusion in Patients With Congestive Heart Failure

Abstract: Intravenous infusion of AM has beneficial hemodynamic and renal effects in patients with CHF.

Cited by 243 publications

References 22 publications

Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in patients with primary aldosteronism

Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in patients with primary aldosteronism

Endogenous Vasoactive Peptides

Biomarkers of Cardiac Injury

Contact Info

Product

Resources

About