Adrenomedullin Mediates Coronary Vasodilation through Adenosine Receptors and KATPChannels

Sabates, Braulio; Pigott, John D.; Choe, Ella U.; Cruz, M.P.; Lippton, Howard; Hyman, Albert L.; Flint, Lewis M.; Ferrara, John J.

doi:10.1006/jsre.1996.4985

Cited by 47 publications

(27 citation statements)

References 10 publications

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“…These findings are consistent with previous reports that a coronary vasodilator effect was induced by AM (24,30,31) and CGRP (32). Thus, AM may exert a cardioprotective effect as shown in CGRP (33,34).…”

Section: Discussionsupporting

confidence: 94%

Regional Hemodynamic Effects of Adrenomedullin in Wistar Rats: A Comparison with Calcitonin Gene-Related Peptide.

et al. 2002

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Section: Discussionsupporting

confidence: 94%

Regional Hemodynamic Effects of Adrenomedullin in Wistar Rats: A Comparison with Calcitonin Gene-Related Peptide.

et al. 2002

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“…These findings suggested that the vasodilator action resulted in part through release of NO and in part through activation of K channels. In anaesthetised open-chested dogs, coronary vasodilatation in response to bolus injection of ADM, into the first diagonal branch of the left anterior descending coronary artery, was blocked by antagonists of adenosine receptors and K ATP channels (Sabates et al, 1997). In porcine preconstricted coronary arteries in vitro, the ADM-induced vasodilatation …”

Section: R De Matteo and Cn Maymentioning

confidence: 98%

Direct coronary vasodilator action of adrenomedullin is mediated by nitric oxide

Matteo

May

2003

British J Pharmacology

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1 Increased circulating levels of adrenomedullin (ADM) cause peripheral vasodilatation and hypotension, accompanied by cardiac actions including tachycardia and increases in cardiac contractility, cardiac output, coronary conductance (CC) and coronary blood flow (CBF). It is unclear to what extent these cardiac effects are direct actions of ADM or secondary to the hypotension and altered cardiac loading. 2 The direct cardiac actions of ADM were examined in conscious sheep previously implanted with aortic and coronary flow probes, and an indwelling left coronary artery cannula. Responses to infusion of ADM (0.5 mg kg À1 h À1 for 1 h) into the left coronary artery or jugular vein were compared (n ¼ 6). The effect of blockade of nitric oxide (NO) synthase with intracoronary (i.c.)), infused for 2 h before and during ADM infusion, was assessed to determine whether the responses to ADM were mediated by NO (n ¼ 5). 3 I.c. ADM caused large and sustained increases in CC (0.3570.07 -0.5570.13 ml min À1 mmHg À1 , Po0.05) and CBF (2876-4279 ml min À1 , Po0.05), but had no effect on arterial pressure or indices of cardiac contractility (first differential of the upstroke of systole and peak aortic flow rate). Intravenous infusion of ADM had no effects. 4 I.c. L-NNA, at a dose that abolished the coronary vasodilator action of acetylcholine, blocked ADM-induced coronary vasodilatation. 5 In conclusion, ADM had a direct coronary vasodilator action that was mediated by release of endogenous NO and resulted in increased CBF. There was no evidence for a direct inotropic action of ADM.

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“…4, A and B). This nonreceptor-mediated action of AM was not surprising as Sabates et al (1997) reported that AM can activate an adenosine receptor. However, a lack of effect of xanthine amine congener, an inhibitor of adenosine receptors, in our experiments (Fig.…”

Section: Discussionmentioning

confidence: 78%

“…The screening of different K ϩ -channels with various antagonists (Fig. 7B) suggests that the target for PKA activation by AM in rat ileum is likely to be the ATP-dependent K ϩ -channels just like in the vascular smooth muscle cells (Sabates et al, 1997).…”

Section: Discussionmentioning

confidence: 98%

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The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with β3-Adrenoceptor in the Serotonin-Induced Muscle Contraction

Kravtsov

Hwang²,

Tang³

2004

The Journal of Pharmacology and Experimental Therapeutics

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In contrast to vascular muscles, the contribution of a hypotensive peptide adrenomedullin (AM) to the regulation of visceral smooth muscles is obscure. The content, synthesis, and effects of AM on the muscular tone in rat ileum were explored. It was found that there was immunoreactive AM (301 pg/mg of protein) and AM mRNA expression (162 fg/pg actin mRNA) in the ileum and that AM evoked relaxation in ileal strips (K i ϭ 0.85 nM) precontracted with serotonin. Antagonists of both AM (AM ) and calcitonin gene-related peptide ) receptors did not affect this AM-induced relaxation, whereas it was suppressed by a selective blocker of ␤ 3 -adrenoreceptor (SR 59230A). The AM-induced relaxation was accompanied by a production of cAMP. Antagonists of protein kinases A (KT 5720 and H-7) and an inhibitor of the ATP-dependent K ϩ -channels (glibenclamide) attenuated the effect of AM. We suggest that AM is a local regulator of the ileal tone, with an inhibitory action on muscle contraction. AM may activate the ␤ 3 -adrenoceptors, resulting in protein kinase A activation, which in turn opens the ATP-dependent K ϩ -channels.The hypotensive peptide, adrenomedullin (AM), was originally purified from both adrenal medulla and pheochromocytoma Kitamura and Eto, 1997;Jougasaki and Burnett, 2000). Two unique structures, a 6-amino acid ring with a disulfide bond and a C-terminal amide in the molecule of AM Hinson et al., 2000;Jougasaki and Burnett, 2000), are likely to determine its vasorelaxation properties. AM shares structural homology with the calcitonin gene-related peptide (CGRP), indicating that AM probably belongs to the CGRP superfamily (Kitamura and Eto, 1997;Hinson et al., 2000;Poyner et al., 2002). The signal transduction pathways have been studied in the greatest detail in the vasculature. A large body of experimental data shows AM synthesis in smooth muscle cells (Kitamura and Eto, 1997;Nishimura et al., 1997) and suggests that AM-induced vasodilation may be mediated by a specific receptor functionally coupled to adenylate cyclase (Eguchi et al., 1994a;Kitamura and Eto, 1997;Nussdorfer et al., 1997;Jougasaki and Burnett, 2000;Poyner et al., 2002). AM-specific receptors are not only found in smooth muscle cells, but also in endothelium cells (Kamitani et al., 1999). It has been reported that the binding of AM to the endothelial receptor can trigger the nitric oxide (NO)-cGMP pathway (Ikeda et al., 1996). Therefore, it is now widely accepted that at least two mechanisms appear to underlie the AM-induced relaxation in vascular muscles: 1) a direct action on vascular smooth muscle cells to increase cAMP (Eguchi et al., 1994a,b;Shimekake et al., 1995;Kitamura and Eto, 1997;Yoshimoto et al., 1998) and 2) an indirect action on endothelial cells to stimulate NO synthesis (Shimekake et al., 1995;Hinson et al., 2000;Jougasaki and Burnett, 2000).The results of mRNA blot analysis reported 10 years ago (Sakata et al., 1993) and later confirmed (Nishimura et al., 1997;Cameron and Fleming, 1998;Sakata et al., 1998) imply that r...

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Adrenomedullin Mediates Coronary Vasodilation through Adenosine Receptors and KATPChannels

Cited by 47 publications

References 10 publications

Regional Hemodynamic Effects of Adrenomedullin in Wistar Rats: A Comparison with Calcitonin Gene-Related Peptide.

Regional Hemodynamic Effects of Adrenomedullin in Wistar Rats: A Comparison with Calcitonin Gene-Related Peptide.

Direct coronary vasodilator action of adrenomedullin is mediated by nitric oxide

The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with β3-Adrenoceptor in the Serotonin-Induced Muscle Contraction

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