Extracellular ATP and bradykinin increase cGMP  in vascular endothelial cells via activation of PKC

Castro, Andrea; Amorena, Carlos; Müller, Angélica; Ottaviano, G; Téllez-Iñón, Marı́a T.; Taquini, Alberto C.

doi:10.1152/ajpcell.1998.275.1.c113

Cited by 17 publications

(15 citation statements)

References 29 publications

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“…Although bradykinin and ATP share the capacity of mobilizing intracellular Ca 2 þ stores, they differ in activation of eNOS in other regulatory aspects. For instance, treatment of cultured aortic endothelial cells with inhibitors of PKC abolished L-NAME-sensitive cGMP production induced by ATP, but not that induced by bradykinin (Castro et al, 1998). In addition, phosphorylation of the Ser 617 and Ser 635 residues of eNOS mediated by PKA in response to bradykinin and ATP in bovine aortic endothelial cells are quantitatively different (Michell et al, 2002).…”

Section: Discussionmentioning

confidence: 97%

Melatonin inhibits nitric oxide production by microvascular endothelial cells in vivo and in vitro

Silva

Tamura

Macedo

et al. 2007

British J Pharmacology

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Background and purpose: We have previously shown that melatonin inhibits bradykinin-induced NO production by endothelial cells in vitro. The purpose of this investigation was to extend this observation to an in vivo condition and to explore the mechanism of action of melatonin. Experimental approach: RT-PCR assays were performed with rat cultured endothelial cells. The putative effect of melatonin upon arteriolar tone was investigated by intravital microscopy while NO production by endothelial cells in vitro was assayed by fluorimetry, and intracellular Ca 2 þ measurements were assayed by confocal microscopy. Key results: No expression of the mRNA for the melatonin synthesizing enzymes, arylalkylamine N-acetyltransferase and hydroxyindole-O-methyltransferase, or for the melatonin MT 2 receptor was detected in microvascular endothelial cells. Melatonin fully inhibited L-NAME-sensitive bradykinin-induced vasodilation and also inhibited NO production induced by histamine, carbachol and 2-methylthio ATP, but did not inhibit NO production induced by ATP or a, b-methylene ATP. None of its inhibitory effects was prevented by the melatonin receptor antagonist, luzindole. In nominally Ca 2 þ -free solution, melatonin reduced intracellular Ca 2 þ mobilization induced by bradykinin (40%) and 2-methylthio ATP (62%) but not Ca 2 þ mobilization induced by ATP. Conclusions and implications:We have confirmed that melatonin inhibited NO production both in vivo and in vitro. In addition, the melatonin effect was selective for some G protein-coupled receptors and most probably reflects an inhibition of Ca 2 þ mobilization from intracellular stores.

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Section: Discussionmentioning

confidence: 97%

Melatonin inhibits nitric oxide production by microvascular endothelial cells in vivo and in vitro

Silva

Tamura

Macedo

et al. 2007

British J Pharmacology

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“…Increasing evidence suggest that NO may also signal through a cGMP independent pathway: NO inhibits the Krebs cycle [42], and inhibits complex I and IV of the mitochondrial respiratory chain [43,44] compromising the mitochondrial function in neurons [45] leading to ATP hydrolysis and subsequent accumulation of adenosine [46,47] that, in turn, can signal through activation of high affinity adenosine receptors (A 1 and A 2A subtypes) or low affinity adenosine receptors (A 2B and A 3 subtypes). Indeed, the inhibition of noradrenaline release induced by NO seems to be mediated by activation (by adenosine) of the adenosine A 1 receptors subtype since the inhibition of noradrenaline release mediated by NO donors was prevented by the adenosine A 1 receptors antagonist (DPCPX) but was not altered by the adenosine A 2A receptors antagonist (SCH 58261).…”

Section: Discussionmentioning

confidence: 99%

Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries

et al. 2015

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Nitric oxide (NO) seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS) inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS) was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells) and Confocal Microscopy. Results indicated that: 1) in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2) in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3) confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.

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“…NO released basally or after stimulation by agonists acts on adjacent smooth muscle cells to activate guanylate cyclase, converting GTP into cGMP, which mediates relaxation [20]. NO also works in an autocrine manner stimulating cGMP production in endothelial cells [21,22]. Lipoproteins, such as LDL, also interact with this system, as they have been shown to down-regulate endothelial cell cGMP production [23,24].…”

Section: Introductionmentioning

confidence: 99%

Chylomicron-remnant-like particles inhibit the basal nitric oxide pathway in porcine coronary artery and aortic endothelial cells

et al. 2003

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The effects of chylomicron remnants on the activity of basally produced nitric oxide (NO) from porcine coronary artery rings and porcine aortic endothelial cells were studied by investigating the effects of chylomicron-remnant-like particles (CMR-LPs) containing porcine apolipoprotein E on the vessel tone of porcine coronary arteries and on cGMP release by aortic endothelial cells. CMR-LPs were oxidized by incubation with CuSO(4) (10 microM) for 18 h at 37 degrees C. N (omega)-nitro-L-arginine (L-NOARG) and oxidized CMR-LPs (oxCMR-LPs), but not native CMR-LPs, increased the vessel tone of static porcine coronary artery rings (increase in tone as a percentage of the tone induced by depolarizing Krebs-Henseleit solution: L-NOARG, 14.24 +/- 2.09; oxCMR-LPs, 4.98 +/- 0.88; and native CMR-LPs, 0.47 +/- 0.21). L-NOARG, endothelium removal and oxCMR-LPs also all significantly increased the maximum relaxation of the vessels to S -nitroso- N -acetyl-DL-penicillamine. In addition, oxCMR-LPs reduced the amounts of cGMP released by porcine aortic endothelial cells into the culture medium from 116 +/- 12.0 to 84.2 +/- 11.6 fmol/microg of cellular protein, mimicking the effects of L-NOARG. These results indicate that oxCMR-LPs, but not native CMR-LPs, inhibit the activity, production or release of NO from unstimulated porcine coronary and aortic endothelial cells. oxCMR-LPs mimicked the addition of L-NOARG and endothelium removal in these experimental systems, suggesting that the lipoproteins were interfering with the L-arginine/NO pathway. This study provides further evidence to support a role of chylomicron remnants in the development of atherosclerosis.

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Extracellular ATP and bradykinin increase cGMP in vascular endothelial cells via activation of PKC

Cited by 17 publications

References 29 publications

Melatonin inhibits nitric oxide production by microvascular endothelial cells in vivo and in vitro

Melatonin inhibits nitric oxide production by microvascular endothelial cells in vivo and in vitro

Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries

Chylomicron-remnant-like particles inhibit the basal nitric oxide pathway in porcine coronary artery and aortic endothelial cells

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