Effects of Adrenomedullin Inhalation on Hemodynamics and Exercise Capacity in Patients With Idiopathic Pulmonary Arterial Hypertension

Nagaya, Noritoshi; Kyotani, Shingo; Uematsu, Masaaki; Ueno, K.; Oya, Hideo; Nakanishi, Norifumi; Shirai, Masamitsu; Mori, Hiromu; Miyatake, Kunio; Kangawa, Kenji

doi:10.1161/01.cir.0000109493.05849.14

Cited by 101 publications

(53 citation statements)

References 39 publications

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“…For this reason, AM has recently been given by inhalation in tests of its potential benefit in PH. With this method of administration, AM led to sustained and selective reduction of pulmonary artery pressure in a surfactant-depleted piglet model (145) and in rats with monocrotaline-induced PH (88) and improved pulmonary hemodynamics and exercise tolerance in patients with IPAH (87).…”

Section: )mentioning

confidence: 99%

Mediators and modulators of pulmonary arterial hypertension

Said¹

2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: )mentioning

confidence: 99%

Mediators and modulators of pulmonary arterial hypertension

Said¹

2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Furthermore, the same group reported that in patients with idiopathic pulmonary arterial hypertension, inhalation of AM lowered pulmonary artery pressure and resistance, improving exercise tolerance. 80 Although the long-term effects need to be examined, this novel approach seems promising for using AM in the treatment of primary pulmonary hypertension, for which few effective medical treatments are currently available.…”

Section: Vascular Protective Effects In Vivomentioning

confidence: 99%

Adrenomedullin

Kato

Tsuruda

Kita

et al. 2005

ATVB

145

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Abstract-Adrenomedullin (AM) is a vasodilator peptide having a wide range of biological actions such as reduction of oxidative stress and inhibition of endothelial cell apoptosis. The AM gene is expressed in vascular walls, and AM was found to be secreted from cultured vascular endothelial cells, smooth muscle cells, and adventitial fibroblasts. Plasma AM levels in patients with arteriosclerotic vascular diseases are elevated in possible association with the severity of the disease. When administered over a relatively short period, AM dilates blood vessels via an endothelium-dependent or independent mechanism. Experiments in vitro have shown that AM exerts multiple actions on cultured vascular cells, which are mostly protective or inhibitory against vascular damage and progression of arteriosclerosis. Key Words: adrenomedullin Ⅲ vasodilatation Ⅲ endothelium Ⅲ smooth muscle cell Ⅲ arteriosclerosis C ardiovascular diseases secondary to arteriosclerosis of blood vessels are currently among the leading causes of death in developed countries. A number of factors, both humoral and mechanical, have been shown to modulate vascular function in humans as well as in experimental animals. 1 Blood vessel dysfunction resulting from an imbalance of those factors accelerates the process of vascular remodeling and atherosclerosis. 1 Vasoconstrictors including angiotensin II and endothelins not always but mostly act as proatherogenic factors, whereas vasodilators, either peptides or non-peptides, such as natriuretic peptides, nitric oxide (NO), and prostaglandin (PG) I 2 , have antiatherogenic properties. 1 In 1993, a new vasodilator peptide, adrenomedullin (AM), was isolated from the tissue extract of a human pheochromocytoma by monitoring cAMP levels in rat platelets. 2 Substantial levels of the AM peptide and gene expression were detected in the cardiovascular tissues including blood vessels. As listed in the Table, AM was found to exert a wide range of biological actions related to vascular functions in cultured cells, with which observations in vivo have been mostly accordant. Ever since the discovery of AM, efforts have been made to clarify the role of this bioactive peptide in blood vessels and a substantial amount of basic and clinical data has been accumulated. In this review, after summarizing the biochemical and pharmacological features of AM, we discuss its role in blood vessels, which is assumed to be protective, or inhibitory against the progression of vascular damage and remodeling. Biochemistry of AMHuman AM is a 52-aa peptide with a ring structure formed by a disulfide bond and amidated tyrosine at the C terminus ( Figure 1), both essential for binding to receptors and biological activity. 2-4 Based on sequence homology, AM is thought to belong to the calcitonin gene-related peptide (CGRP) superfamily. [2][3][4] Cloning of the cDNA encoding AM revealed the AM precursor peptide preproAM to comprise 185 amino acids, with the C terminus followed by a pair of basic amino acids, Arg-Arg, a typical processing signal (...

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“…Also it is a new tool for use in diagnosis of extracellular volume in renal insufficiency [63]. AM seems to have the potential to protect organs from damage, since AM supplementation was effective to improve hemodynamics in patients with congestive heart failure and hypertension [64][65][66][67].…”

Section: Ammentioning

confidence: 99%

Adrenomedullin and its Related Peptide

Shimosawa

Fujita

2005

Endocr J

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MORE than 100 years have passed since Riva-Rocci [1] modified the sphygmograph by Marey [2], Mahomed [3] and Von Basch [4] to make conventional blood pressure measurements possible. Two years after the method was established, existence of hypertensive agents, now known as renin, was reported [5]. Since then laboratory investigations as well as clinical and epidemiological studies in hypertension research have been advancing at an exponential rate [6]. Since the 1950s, several circulation-regulating peptides, both hypertensive and hypotensive, were discovered. Among them, a novel vasodilative peptide, adrenomedullin (AM) was isolated from pheochromocytoma tissue in 1993 [7]. Another processing site in a propeptide of AM was found and a new hypotensive peptide, named proadrenomedullin N-terminal 20 peptide (PAMP), was isolated from human plasma and urine [7,8].Blood circulates throughout the body by the pressure force generated by cardiac output and peripheral resistance. Each of these primary determinants of blood pressure is determined by the interaction of an exceedingly complex series of factors. Thus it is crucial to determine this complex of interactions in order to better understand the physiological role of these newly found factors. AM and PAMPAs mentioned above, AM, originally isolated from pheochromocytoma cell, is also produced and secreted in endothelial cells [7,19], and has been shown to exhibit hypotensive action by direct vasodilation via both the elevation of intracellular cAMP and alteration of calcium sensitivity in vascular smooth muscle cells [20]. Besides these actions, recent studies have shown that AM increases nitric oxide synthesis in endothelial cell by elevating intracellular calcium [21][22][23][24]. Studies on the physiological action of AM have also revealed that AM increases intracellular cAMP [22] [28]. Moreover, AM inhibits smooth muscle cell migration and proliferation [29, 30]. AM also shares a slight homology with CGRP and the above mentioned physiological effects are inhibited by CGRP antagonist CGRP(8-37) [21]. Together with the evidence that AM production is increased in failing heart [31, 32], it is speculated that

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Effects of Adrenomedullin Inhalation on Hemodynamics and Exercise Capacity in Patients With Idiopathic Pulmonary Arterial Hypertension

Cited by 101 publications

References 39 publications

Mediators and modulators of pulmonary arterial hypertension

Mediators and modulators of pulmonary arterial hypertension

Adrenomedullin

Adrenomedullin and its Related Peptide

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