Specific receptors for adrenomedullin in cultured rat vascular smooth muscle cells

Eguchi, Satoru; Hirata, Yukio; Kano, Hiroaki; Sato, Kyoko; Watanabe, Yukihiko; Watanabe, Takushi X.; Nakajima, Kiichiro; Sakakibara, Shumpei; Marumo, Fumiaki

doi:10.1016/0014-5793(94)80143-6

Cited by 282 publications

(122 citation statements)

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“…In fact, there is much difference among species in the vasodilating effect, in cAMP production, and in the affinity of adrenomedullin. 29,31 A significant antiapoptotic effect of adrenomedullin was observed at 10 Ϫ7 mol/L. Baseline adrenomedullin levels in the culture medium of HUVECs were substantially low.…”

Section: Discussionmentioning

confidence: 93%

“…1 Adrenomedullin is believed to promote the relaxation of vascular smooth muscle cells through a cAMP/ protein kinase A pathway. 29 Adrenomedullin also elevates intracellular cAMP level in other cell types, including endothelial cells. 30 In the present study, cAMP analogs or a cAMP-elevating reagent failed to mimic the antiapoptotic effect of adrenomedullin.…”

Section: Discussionmentioning

confidence: 99%

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Adrenomedullin and Nitric Oxide Inhibit Human Endothelial Cell Apoptosis via a Cyclic GMP-Independent Mechanism

et al. 2000

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Adrenomedullin and Nitric Oxide Inhibit Human Endothelial Cell Apoptosis via a Cyclic GMP-Independent Mechanism

et al. 2000

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“…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

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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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“…This caused a transient increase (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) in perfusion pressure. The preparations were then rinsed with SD-free Krebs solution for 1 h.…”

Section: Chemical Removal Of Vascular Endotheliummentioning

confidence: 99%

Effect of Adrenomedullin on Adrenergic Vasoconstriction in Mesenteric Resistance Arteries of the Rat

et al. 2005

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Abstract. Adrenomedullin (AM) is a hypotensive peptide that belongs to a family of peptides structurally related to calcitonin gene-related peptide (CGRP). The present study examined the effect of AM on adrenergic nerve-mediated vasoconstriction in rat perfused mesenteric vascular beds without endothelium. Perfusion of AM at 0.1 nM but not 10 nM increased vasoconstrictor responses to periarterial nerve stimulation (PNS) (1 -4 Hz), while AM at 10 nM significantly attenuated vasoconstriction induced by bolus injection of norepinephrine (NE). In preparations treated with capsaicin (a CGRP depletor), pressor responses to both PNS and NE injection were markedly attenuated by AM. Perfusion of CGRP(8 -37) (a CGRP-receptor antagonist) significantly potentiated the PNS-but not the NE-induced vasoconstriction. Combined perfusion of CGRP(8 -37) and AM had no effect on the PNS-induced response and antagonized the inhibitory effect of AM on the NE-induced response. AM(22 -52) (an AM-receptor antagonist) did not influence the effect of AM. These findings suggest that AM facilitates adrenergic vasoconstriction by inhibiting neurotransmission of CGRP-containing nerves, which counteract adrenergic nerve-mediated vasoconstriction.

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Specific receptors for adrenomedullin in cultured rat vascular smooth muscle cells

Cited by 282 publications

References 11 publications

Adrenomedullin and Nitric Oxide Inhibit Human Endothelial Cell Apoptosis via a Cyclic GMP-Independent Mechanism

Adrenomedullin and Nitric Oxide Inhibit Human Endothelial Cell Apoptosis via a Cyclic GMP-Independent Mechanism

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

Effect of Adrenomedullin on Adrenergic Vasoconstriction in Mesenteric Resistance Arteries of the Rat

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