Distribution and characterization of immunoreactive rat adrenomedullin in tissue and plasma

Sakata, Junichiro; Shimokubo, Toru; Kïtamura, Kazuo; Nishizono, Masatoshi; Iehiki, Yoshinari; Kangawa, Kenji; Matsuo, Hisayuki; Eto, Tanenao

doi:10.1016/0014-5793(94)00928-7

Cited by 266 publications

(143 citation statements)

References 9 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…This finding was inconsistent with previous research in which a high concentration of immunoreactive ADM was found ubiquitously in all pulmonary tissue examined, including VSMCs and ECs, 6 and a high expression level of ADM mRNA was found in the lungs as well as in the adrenal glands. [7][8][9] This discrepancy can be explained by the possibility that ADM and ADT are synthesized by ECs and VSMCs as well, and that which is biosynthesized in the ECs is rapidly and continuously secreted into the blood or functions as an autocrine or paracrine regulator. 10 However, the ADM and ADT that is synthesized by VSMCs may be stored in the smooth muscle cell layer.…”

Section: Discussionmentioning

confidence: 99%

Changes and Distributions of Peptides Derived From Proadrenomedullin in Left-to-Right Shunt Pulmonary Hypertension of Rats

Zhao

Wang

Gao

et al. 2008

Circ J

View full text Add to dashboard Cite

ulmonary hypertension (PHT) is a common and serious complication of left-to-right shunt congenital heart disease (CHD), and the risk and mortality of cardiac surgery in CHD patients complicated with serious PHT are significantly increased. However, the pathogenesis of PHT remains unclear so far.Adrenomedullin (ADM), a potent vasodilation peptide, was originally isolated from human pheochromocytoma and is thought to have an autocrine or paracrine action, playing an important role in the regulation of vascular tone. Later, it was found that its precursor preproadrenomedullin (preproADM) consists of 185 amino acids in length and is cleaved into 4 active peptides by endogenous protease: ADM, adrenotensin (ADT), proadrenomedullin N-terminal 20 peptide (PAMP) and proADM45-92. 1,2 The relationship between the 4 peptides and PHT is being investigated and in the present study, we investigated the changes and distribution of the peptides derived from proADM in a rat model of PHT. Methods Animal Model PreparationMale Wistar rats (n=21, body weight 140-160 g) were randomly divided into a Control group (n=12) and Experiment group (n=9). The study met the National Research Council's Guide for the care and use of laboratory animals.In the Experiment group, a left common carotid artery to external jugular vein shunt operation was performed to establish a left-to-right shunt model. 3 Animals were anesthetized with 0.25% pentobarbital sodium (40 mg/kg ip) and heparin (0.5 mg/kg) was used to prevent solidification. The left common carotid artery and left external jugular vein were connected by a sterilized cuff. Postoperatively, there was obvious pulsation and bulging of the proximal cardiac part of the external jugular vein and the oxygen saturation had increased from 81±4.7% to 91±5.6%, indicating smooth Circ J 2008; 72: 476 -481 (Received May 22, 2007; revised manuscript received November 5, 2007; accepted November 13, 2007 Background Pulmonary hypertension (PHT) is a common complication of congenital heart disease and the pulmonary vascular structural remodeling because of the high pulmonary blood flow is considered to be the key pathologic process. In the present study the change and distribution of peptides derived from proadrenomedullin in a rat model of PHT caused by a left-to-right shunt were measured to elucidate the mechanism. Methods and Results Twelve weeks after a cervical shunt was established by a cuff technique in an experimental group of rats, the systolic pulmonary artery pressure (sPAP) was measured by catheterization. Morphologic assessment included the measurement of the weight ratio of the right ventricle (RV) to the left ventricle plus septum (LV+SP) and the mean percentage of media wall thickness (MT%) in moderate-sized pulmonary arteries. The distribution of adrenomedullin (ADM), adrenotensin (ADT) and proadrenomedullin N-terminal 20 peptide (PAMP) were measured by immunohistochemical staining. The mRNA expressions of ADM, ADT, PAMP and proADM45-92 were investigated by reverse transcription polymerase ch...

show abstract

Section: Discussionmentioning

confidence: 99%

Changes and Distributions of Peptides Derived From Proadrenomedullin in Left-to-Right Shunt Pulmonary Hypertension of Rats

Zhao

Wang

Gao

et al. 2008

Circ J

View full text Add to dashboard Cite

show abstract

“…Recent studies clarified that adrenomedullin is synthesized in various tissues, including vascular smooth muscles, glomerular mesangium, cardiac tissues and lungs [2,3,16]. Adrenomedullin has vasodilator and antiproliferative effects in vascular smooth muscle cells and mesangial cells [2,7].…”

Section: Hormonal Assaysmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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

Nakamura¹,

Honda²,

Ishikawa³

et al. 1998

Endocr J

Self Cite

View full text Add to dashboard Cite

Abstract.The present study was undertaken to determine plasma adrenomedullin levels in patients with non-insulin dependent diabetes mellitus (NIDDM) to elucidate the potential involvement in the pathogenesis of diabetic complications. The patients were 24 males and 21 females with ages of 55 ± 2.1 years (mean ± SEM). Plasma adrenomedullin levels were 5.94 ± 0.44 pmol/l in patients with NIDDM, and were not affected by plasma glucose concentration.

show abstract

“…10 Immunoreactive AM has subsequently been detected in plasma and a variety of tissues, including blood vessels and lungs. 11,12 It has been reported that there are abundant binding sites for AM in the lungs. 13 We have shown that the plasma AM level increases in proportion to the severity of pulmonary hypertension and that circulating AM is partially metabolized in the lungs.…”

mentioning

confidence: 99%

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

et al. 2004

Self Cite

View full text Add to dashboard Cite

Background-Adrenomedullin (AM) is a potent pulmonary vasodilator peptide. However, whether intratracheal delivery of aerosolized AM has beneficial effects in patients with idiopathic pulmonary arterial hypertension remains unknown. Accordingly, we investigated the effects of AM inhalation on pulmonary hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial hypertension. Methods and Results-Acute hemodynamic responses to inhalation of aerosolized AM (10 g/kg body wt) were examined in 11 patients with idiopathic pulmonary arterial hypertension during cardiac catheterization. Cardiopulmonary exercise testing was performed immediately after inhalation of aerosolized AM or placebo.

show abstract

Distribution and characterization of immunoreactive rat adrenomedullin in tissue and plasma

Cited by 266 publications

References 9 publications

Changes and Distributions of Peptides Derived From Proadrenomedullin in Left-to-Right Shunt Pulmonary Hypertension of Rats

Changes and Distributions of Peptides Derived From Proadrenomedullin in Left-to-Right Shunt Pulmonary Hypertension of Rats

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

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

Contact Info

Product

Resources

About