Norepinephrine-induced contraction of isolated rabbit  bronchial artery: role of α<sub>1</sub>- and α<sub>2</sub>-adrenoceptor activation

Zschauer, A.; Sielczak, M. W.; Smith, David; Wanner, Adam

doi:10.1152/jappl.1997.82.6.1918

Cited by 33 publications

(34 citation statements)

References 24 publications

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“…E and NE, the major hormones released under stress conditions, can bind to specific α- or β-AR [35], [36], [37]. We investigated whether CRS-induced CRC growth is dependent on AR.…”

Section: Resultsmentioning

confidence: 99%

Effect of Chronic Restraint Stress on Human Colorectal Carcinoma Growth in Mice

et al. 2013

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Stress alters immunological and neuroendocrinological functions. An increasing number of studies indicate that chronic stress can accelerate tumor growth, but its role in colorectal carcinoma (CRC) progression is not well understood. The aim of this study is to investigate the effects of chronic restraint stress (CRS) on CRC cell growth in nude mice and the possible underlying mechanisms. In this study, we showed that CRS increased the levels of plasma catecholamines including epinephrine (E) and norepinephrine (NE), and stimulated the growth of CRC cell-derived tumors in vivo. Treatment with the adrenoceptor (AR) antagonists phentolamine (PHE, α-AR antagonist) and propranolol (PRO, β-AR antagonist) significantly inhibited the CRS-enhanced CRC cell growth in nude mice. In addition, the stress hormones E and NE remarkably enhanced CRC cell proliferation and viability in culture, as well as tumor growth in vivo. These effects were antagonized by the AR antagonists PHE and PRO, indicating that the stress hormone-induced CRC cell proliferation is AR dependent. We also observed that the β-AR antagonists atenolol (ATE, β1- AR antagonist) and ICI 118,551 (ICI, β2- AR antagonist) inhibited tumor cell proliferation and decreased the stress hormone-induced phosphorylation of extracellular signal-regulated kinases-1/2 (ERK1/2) in vitro and in vivo. The ERK1/2 inhibitor U0126 also blocked the function of the stress hormone, suggesting the involvement of ERK1/2 in the tumor-promoting effect of CRS. We conclude that CRS promotes CRC xenograft tumor growth in nude mice by stimulating CRC cell proliferation through the AR signaling-dependent activation of ERK1/2.

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“…E and NE, the major hormones released under stress conditions, can bind to specific α- or β-AR [35], [36], [37]. We investigated whether CRS-induced CRC growth is dependent on AR.…”

Section: Resultsmentioning

confidence: 99%

Effect of Chronic Restraint Stress on Human Colorectal Carcinoma Growth in Mice

et al. 2013

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“…Furthermore, a nonselective NOS inhibitor, but not the relatively selective inhibitor of inducible NOS (NOS II) aminoguanidine, augmented PE constriction in PA rings, implicating other NOS isoforms (e.g., NOS III) as the source of NO responsible for this effect (26). Use of the NOS inhibitor, L-NAME, or removal of the endothelium also augmented ␣ 1 -adrenergic vasoconstriction to NE in rabbit bronchial arteries (34). Pretreatment with S-nitrosylating agents including S-nitroso-N-acetylpeni- Fig.…”

Section: Discussionmentioning

confidence: 96%

S-nitrosoglutathione inhibits α₁-adrenergic receptor-mediated vasoconstriction and ligand binding in pulmonary artery

Nozik‐Grayck¹,

Whalen²,

Stamler³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Endogenous nitric oxide donor compounds (S-nitrosothiols) contribute to low vascular tone by both cGMP-dependent and -independent pathways. We have reported that S-nitrosoglutathione (GSNO) inhibits 5-hydroxytryptamine (5-HT)-mediated pulmonary vasoconstriction via a cGMP-independent mechanism likely involving S-nitrosylation of its G proteincoupled receptor (GPCR) system. Because catecholamines, like 5-HT, constrict lung vessels via a GPCR coupled to G q, we hypothesized that S-nitrosothiols modify the ␣ 1-adrenergic GPCR system to inhibit pulmonary vasoconstriction by receptor agonists, e.g., phenylephrine (PE). Rat pulmonary artery rings were pretreated for 30 min with and without an S-nitrosothiol, either GSNO or S-nitrosocysteine (CSNO), and constricted with sequential concentrations of PE (10 Ϫ8 -10 Ϫ6 M). Effective cGMP-dependence was tested in rings pretreated with soluble guanylate cyclase inhibitors {either 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or LY-83583} or G kinase inhibitor (KT-5823), and a thiol reductant [dithiothreitol (DTT)] was used to test reversibility of S-nitrosylation. Both S-nitrosothiols attenuated the PE dose response. The GSNO effect was not prevented by LY-83583, ODQ, or KT-5823, indicating cGMP independence. GSNO inhibition was reversed by DTT, consistent with S-nitrosylation or other GSNOmediated cysteine modifications. In CSNO-treated lung protein, the ␣ 1-adrenergic receptor was shown to undergo S-nitrosylation in vitro using a biotin switch assay. Studies of ␣1-adrenergic receptor subtype expression and receptor density by saturation binding with 125 I-HEAT showed that GSNO decreased ␣1-adrenergic receptor density but did not alter affinity for antagonist or agonist. These data demonstrate a novel cGMP-independent mechanism of reversible ␣1-adrenergic receptor inhibition by S-nitrosothiols. nitric oxide; S-nitrosylation; G protein-coupled receptor; guanosine 3Ј,5Ј-cyclic monophosphate THE LOW-RESISTANCE PULMONARY VASCULAR CIRCUIT is regulated by multiple neural, humoral, and endocrine factors among which the endothelium-derived relaxing factor, nitric oxide (NO), plays a fundamental role. NO bioactivity in the pulmonary circulation is present in the form of NO donor compounds (S-nitrosothiols) that maintain low vascular tone by both cGMP-dependent and -independent pathways (13). NO released from endothelial cells activates guanylate cyclase in vascular smooth muscle cells to increase cGMP levels, which in turn relaxes vascular smooth muscle. NO also exerts cGMPindependent effects on the smooth muscle including (but not limited to) stimulating Na ϩ -K ϩ -ATPase activity, modifying K ϩ and Ca 2ϩ channels, and decreasing the sensitivity to, or release of, vasoconstrictors (1,6,12,17,24).We previously demonstrated that pulmonary vasoconstriction elicited by serotonin (5-hydroxytryptamine, 5-HT) is reversibly inhibited by the NO donor S-nitrosoglutathione (GSNO) (23). In addition, use of nitric oxide synthase (NOS) inhibitors or removal of the endothelium to decrease NO...

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“…In addition, there are reports that endothelial α 2 ‐adrenoceptors mediate vasodilatation, which would tend to attenuate vasoconstriction resulting from the activation of α 1 ‐ARs by noradrenaline (Zschauer et al . ; Thorin et al . ; Figueroa et al .…”

Section: Discussionmentioning

confidence: 99%

Double disruption of α_2A‐ and α_2C‐adrenoceptors induces endothelial dysfunction in mouse small arteries: role of nitric oxide synthase uncoupling

Couto

Davel

Brum

et al. 2014

Experimental Physiology

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New Findings r What is the central question of this study?Knockout mice lacking both α 2A -and α 2C -adrenergic receptors (α 2A /α 2C -ARKO) provide a model for understanding the mechanisms underlying the deleterious effects of sympathetic hyperactivity on the cardiovascular system. The purpose of this study was to compare the effects of sympathetic hyperactivity on the vascular reactivity of large and small arteries from α 2A /α 2C -ARKO mice and to evaluate the role of nitric oxide and oxidative stress. r What is the main finding and its importance?We show that sympathetic hyperactivity alters vascular reactivity only in small arteries. Uncoupling endothelial nitric oxide synthase may be a significant source of superoxide anion and reduced NO bioavailability in small arteries from α 2A /α 2C -ARKO mice, increasing the contractile tone. Knockout mice lacking both α 2A -and α 2C -adrenergic receptors (α 2A /α 2C -ARKO) provide a model for understanding the mechanisms underlying the deleterious effects of sympathetic hyperactivity on the cardiovascular system. Thus, in the present study we investigated the vascular reactivity of large and small arteries of α 2A /α 2C -ARKO mice. Aorta and mesenteric small arteries (MSAs) from 7-month-old male α 2A /α 2C -ARKO mice and congenic C57BL6/J mice (wild-type, WT) were studied. In the aorta, noradrenaline-and serotonin-induced contraction was similar between groups, but in MSAs there was an increase in agonist-induced contraction in α 2A /α 2C -ARKO compared with WT. The l-NAME effect was reduced in MSAs of α 2A /α 2C -ARKO mice compared with WT mice, as was basal NO evaluated by a 4,5-diaminofluorescein diacetate probe. Increased total endothelial nitric oxide synthase (eNOS) protein expression was observed in MSAs from α 2A /α 2C -ARKO mice, while the dimer/monomer ratio of eNOS was decreased. Mesenteric small arteries from α 2A /α 2C -ARKO mice showed an increase in ethidium bromide-positive nuclei, indicating oxidative stress, which was attenuated by incubation with l-NAME. The sympathetic hyperactivity present in α 2A /α 2C -ARKO mice alters vascular reactivity only in certain types of arteries. Moreover, after chronic sympathetic hyperactivity, uncoupling eNOS may be a significant source of superoxide anion and reduced NO bioavailability in small vessels, increasing the contractile tone.

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Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of α₁- and α₂-adrenoceptor activation

Cited by 33 publications

References 24 publications

Effect of Chronic Restraint Stress on Human Colorectal Carcinoma Growth in Mice

Effect of Chronic Restraint Stress on Human Colorectal Carcinoma Growth in Mice

S-nitrosoglutathione inhibits α₁-adrenergic receptor-mediated vasoconstriction and ligand binding in pulmonary artery

Double disruption of α_2A‐ and α_2C‐adrenoceptors induces endothelial dysfunction in mouse small arteries: role of nitric oxide synthase uncoupling

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Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of α1- and α2-adrenoceptor activation

Cited by 33 publications

References 24 publications

Effect of Chronic Restraint Stress on Human Colorectal Carcinoma Growth in Mice

Effect of Chronic Restraint Stress on Human Colorectal Carcinoma Growth in Mice

S-nitrosoglutathione inhibits α1-adrenergic receptor-mediated vasoconstriction and ligand binding in pulmonary artery

Double disruption of α2A‐ and α2C‐adrenoceptors induces endothelial dysfunction in mouse small arteries: role of nitric oxide synthase uncoupling

Contact Info

Product

Resources

About

Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of α₁- and α₂-adrenoceptor activation

S-nitrosoglutathione inhibits α₁-adrenergic receptor-mediated vasoconstriction and ligand binding in pulmonary artery

Double disruption of α_2A‐ and α_2C‐adrenoceptors induces endothelial dysfunction in mouse small arteries: role of nitric oxide synthase uncoupling