Roles of different peptide fragments derived from proadrenomedullin in the regulation of vascular tone in isolated rat aorta

Li, Juxiang; Ren, Yanling; Dong, Xiao; Zhong, Guangzhen; Sheng-ying, WU; Tang, Chaoshu

doi:10.1016/s0196-9781(03)00109-8

Cited by 10 publications

(6 citation statements)

References 25 publications

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“…In cultured rat vascular smooth muscle cells, 10 -7 mol/L ADT increased 3 H-TdR incorporation [9] . However, in the study by Li et al, ADT did not alter the vasorelaxant response to ADM in rat aortic rings, and it had no effect on the vascular tone under either resting or preconstricted conditions [10] . It is uncertain if the results relied on species or the vessels used in the different experiments.…”

Section: Discussionmentioning

confidence: 84%

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Effect of adrenotensin on cell proliferation is mediated by angiotensin II in cultured rat mesangial cells

et al. 2009

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Aim: Both adrenomedullin (ADM) and adrenotensin (ADT) are derived from the same propeptide precursor, and both act as circulating hormones and local paracrine mediators with multiple biological activities. Compared with ADM, little is known about how ADT achieves its functions. In the present study, we investigated the effect of ADT on cell proliferation and transforming growth factor-β (TGF-β) secretion in cultured renal mesangial cells (MCs) and determined whether angiotensin II (Ang II) was involved in mediating this process. Methods: Cell proliferation was measured by bromodeoxyuridine (BrdU) incorporation assay, Ang II levels were assayed using an enzyme immunoassay, and real time PCR was used to measure Ang II type 1 (AT1) receptor, Ang II type 2 (AT2) receptor, angiotensinogen (AGT), renin, angiotensin converting enzyme (ACE) and TGF-β1 mRNA levels. TGF-β1 and collagen type IV protein levels in cell media were measured using enzyme-linked immunoassays. Results: ADT treatment induced cell proliferation in a concentration-dependent manner; it also increased the levels of TGF-β1 mRNA and protein as well as collagen type IV excretion by cultured MCs. ADT treatment increased renin and AGT mRNAs as well as Ang II protein, but did not affect the ACE mRNA level. ADT up-regulated angiotensin AT1 receptor mRNA, but not that of the AT2 receptor. The angiotensin AT1 receptor antagonist losartan blocked the effects of ADT-induced cell proliferation, TGF-β1 and collagen type IV synthesis and secretion. Conclusion: ADT has a stimulating role in cell proliferation in cultured MCs. Increases in the levels of Ang II and the AT1 receptor after ADT treatment mediate the stimulating effects of ADT on cell proliferation and extracellular matrix synthesis and secretion.

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Section: Discussionmentioning

confidence: 84%

“…Effect of adrenotensin on cell proliferation is mediated by angiotensin II in cultured rat mesangial cells peptide also stimulates cAMP production in vascular tissue, suggesting that it could have a vasodilating effect under some circumstances [10] .…”

Section: Introductionmentioning

confidence: 99%

Effect of adrenotensin on cell proliferation is mediated by angiotensin II in cultured rat mesangial cells

et al. 2009

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“…21 It was also reported that PAMP antagonizes the stimulatory effect of ADM on endothelial NO production, suggesting a more complex relationship of PAMP and ADM in the regulation of vascular tone. 22 …”

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

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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...

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“…PAMP is a small peptide that is produced during post-transcriptional splicing of preproadrenomedullin and has numerous actions to complement or antagonize AM signaling [50-53]. For two of the reported Adm deficient mouse lines, the design of the targeted allele could not rule out whether the observed phenotypes in the KO animals were due to loss of AM, PAMP, or both [30, 31].…”

Section: Developmentmentioning

confidence: 99%

Adrenomedullin Function in Vascular Endothelial Cells: Insights from Genetic Mouse Models

Karpinich

Hoopes²,

Kechele³

et al. 2011

CHYR

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Adrenomedullin is a highly conserved peptide implicated in a variety of physiological processes ranging from pregnancy and embryonic development to tumor progression. This review highlights past and present studies that have contributed to our current appreciation of the important roles adrenomedullin plays in both normal and disease conditions. We provide a particular emphasis on the functions of adrenomedullin in vascular endothelial cells and how experimental approaches in genetic mouse models have helped to drive the field forward.

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Roles of different peptide fragments derived from proadrenomedullin in the regulation of vascular tone in isolated rat aorta

Cited by 10 publications

References 25 publications

Effect of adrenotensin on cell proliferation is mediated by angiotensin II in cultured rat mesangial cells

Effect of adrenotensin on cell proliferation is mediated by angiotensin II in cultured rat mesangial cells

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

Adrenomedullin Function in Vascular Endothelial Cells: Insights from Genetic Mouse Models

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