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

Akiyama, Shinji; Hatanaka, Yukako; Hobara, Norio; Jin, Hang; Kosugi, Keiji; Takayama, Fusako; Kawasaki, Hiromu

doi:10.1254/jphs.fpj05007x

Cited by 7 publications

(3 citation statements)

References 24 publications

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“…In this study, the inhibitory effects of adrenomedullin on the depolarization-induced contraction were blocked by the receptor antagonist CGRP 8–37 , but not by adrenomedullin 22–52 . In the perfused rat mesenteric artery, adrenomedullin at low concentrations (0.1 n M ), but not higher concentrations, potentiated adrenergic vasoconstriction by inhibiting neurotransmission of CGRP-containing nerves, which counteract adrenergic nerve-mediated vasoconstriction [18]. However, in this study, adrenomedullin had inhibited the contraction induced by depolarization by external high potassium.…”

Section: Discussioncontrasting

confidence: 54%

Cyclic AMP-Independent CGRP8–37-Sensitive Receptors Mediate Adrenomedullin-Induced Decrease of CaCl2-Contraction in Pregnant Rat Mesenteric Artery

Ross

Yallampalli²,

Yallampalli³

2007

J Vasc Res

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Objectives: We tested the hypothesis that adrenomedullin reduces calcium influx independent of potassium channels in depolarized endothelium-denuded mesenteric artery from pregnant rats. Results: Adrenomedullin reduced the CaCl₂-induced contraction, while the receptor antagonist calcitonin gene-related peptide (CGRP)_8–37, but not adrenomedullin_22–52, reversed these effects. Adenylate cyclase inhibition by SQ22536 did not prevent adrenomedullin effects on CaCl₂-induced contraction. Adrenomedullin did not inhibit depolarization-induced calcium entry to isolated vascular smooth muscle. Inhibition of myosin light-chain (MLC) phosphatase by calyculin A reversed the effects of adrenomedullin on contraction caused by submillimolar concentrations of CaCl₂, while adrenomedullin still inhibited contraction caused by higher concentrations of CaCl₂. However, the ratio of phosphorylated to total myosin phosphatase target 1, the regulatory subunit of MLC phosphatase, did not change with adrenomedullin, indicating a lack of MLC phosphatase activation. Interestingly, sodium fluoride, a nonspecific protein phosphatase inhibitor, completely blocked the effect of adrenomedullin on CaCl₂-induced contraction. Adrenomedullin inhibited calcium mobilization from intracellular stores induced by thapsigargin. Conclusion: Adrenomedullin inhibits CaCl₂-induced contraction, without affecting calcium influx, through a CGRP_8–37-sensitive receptor, but not using the cyclic adenosine monophosphate pathway, probably through activation of protein phosphatases. Inhibition of intracellular calcium release is an additional role played by adrenomedullin in calcium homeostasis in vascular smooth muscle.

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Section: Discussioncontrasting

confidence: 54%

Cyclic AMP-Independent CGRP8–37-Sensitive Receptors Mediate Adrenomedullin-Induced Decrease of CaCl2-Contraction in Pregnant Rat Mesenteric Artery

Ross

Yallampalli²,

Yallampalli³

2007

J Vasc Res

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“…Beyond itsaction on endothelial permeability, AM comprises important effects on the vasculars ystem. Cumulating evidence demonstratesincreased nitricoxide release, vasodilatationindifferent vascularbeds, andsubsequent hypotension due to AM (95,99,104,114,(126)(127)(128)(129)(130). With respect to hypotension in severe infection andsepsisitisnoteworthy that septicmice over-expressing AM in their vasculatureare resistanttoendotoxin shockdespitehypotension (127).…”

Section: Adrenomedullin -Actiononthe Endothelium Andvascular System Bmentioning

confidence: 99%

Adrenomedullin and endothelial barrier function

Temmesfeld-Wollbrück

Hocke²,

Suttorp³

et al. 2007

Thromb Haemost

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SummaryAlthough loss of endothelial barrier function is a hallmark of every acute inflammation and contributes to fatal loss of organ function during severe infections, there is no sufficient therapy for stabilization of endothelial barrier function. Endogenous peptide adrenomedullin (AM) serum levels were shown to be increased during severe infection including sepsis and septic shock. In different in-vitro and in-vivo models AM acted as a potent therapeutic endothelial barrier function-stabilizing agent. Activation of specific receptors by AM results in elevation of second messenger cAMP. AM inhibits actin-myosin based endothelial cell contraction and junctional disassembly, thereby preventing paracellular permeability and oedema formation. The peptide furthermore possesses several protective cardiovascular qualities, including protection of the microcirculation during inflammation, and was proven as an efficient counter-regulatory molecule in various models of sepsis and septic shock. Overall, AM may be an attractive molecule to combat against cardiovascular malfunction during severe infection.

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“…Akiyama et al, (24) demonstrated that endo CL internalization as a result of AM introduction could be blocked by both AM and CGRP antagonists (AM22-52 and CGRP8-37) and that desensitized receptor due to binding to AM was also desensitized against CGRP. Akiyama et al (25) suggested that, the receptor was desensitized against both of these two peptides, regardless of with which it encounters. Also previous studies revealed that AM presynaptically inhibits the neurotransmission of rat mesenteric resistance arteries in perivascular CGRPergic nerves, possibly by reducing CGRP release.…”

Section: Discussionmentioning

confidence: 99%

Plasma Adrenomedullin Levels In Patients With Migraine During Naturel Attack And Attack Free Period

et al. 2016

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The role of Calcitonin gene related peptide (CGRP) in migraine has been demonsrated. The aim of this study was to examine the role of Adrenomedullin (AM) which is a member of the calcitonin/CGRP/amylin family in migraine patients during naturel attack and attack free period.Material and Method: Twenty-six migraine patients (11 with aura, 15 without aura) and 26 healty participants were involved. Blood samples were obtained from each patient in attack and attack free period, then compared with each other and control group.Results: Mean plasma AM levels were 19 pmol/l during migraine attacks, 25.23 pmol/l between attacks, and 33.01 pmol/l in the control group. AM levels of migraine patients were significantly lower than controls during non-attack periods (p=0.001) and more interestingly, it further decreased during attack periods (p=0.001). A comparison of the mean plasma AM levels of migraine with and without aura cases revealed the same statistically significant difference (p=0.001). Conclusion:The persistently low AM levels in migraine patients gave the impression that in physiological conditions there may be a balance between CGRP and AM and this may be changed towards to the site of CGRP in migraine pathophysiology while causing a decline in AM levels as we had found. Further studies regarding on AM involvement in migraine pathophysiology are needed to confirm these results.

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

Cited by 7 publications

References 24 publications

Cyclic AMP-Independent CGRP<sub>8–37</sub>-Sensitive Receptors Mediate Adrenomedullin-Induced Decrease of CaCl<sub>2</sub>-Contraction in Pregnant Rat Mesenteric Artery

Cyclic AMP-Independent CGRP<sub>8–37</sub>-Sensitive Receptors Mediate Adrenomedullin-Induced Decrease of CaCl<sub>2</sub>-Contraction in Pregnant Rat Mesenteric Artery

Adrenomedullin and endothelial barrier function

Plasma Adrenomedullin Levels In Patients With Migraine During Naturel Attack And Attack Free Period

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