The Interaction between Endothelium-Derived Relaxing Factor (EDRF) and Eicosanoids in the Regulation of the Mesenteric Microcirculation

Kodama, Teruaki; Marmon, Louis M.; Vargas, Roberto; Farhat, Michel Y.; Hoy, Gregory R.; Ramwell, Peter W.

doi:10.1006/jsre.1995.1035

Cited by 8 publications

(5 citation statements)

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“…The observation that NO synthesis inhibition increased NA‐induced contractions is in agreement with a previous report that L‐NAME potentiated the vasoconstrictor response to NA in rat isolated mesenteric arteries (Kodama et al , 1995). In addition, and as observed after endothelium removal, the increase in NA‐induced constrictor responses due to NOs inhibition was abolished by indomethacin, but not by NDGA.…”

Section: Discussionsupporting

confidence: 92%

Effects of eicosanoids and nitric oxide on the noradrenaline‐induced contractions in the rat mesenteric bed

Peredo

Adler‐Graschinsky

2000

J. Autonom. Pharmacol.

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1. The effects of the inhibition of the metabolism of arachidonic acid (AA) on the constrictor responses to noradrenaline (NA) were studied in the rat perfused mesenteric bed. The inhibitor of all the pathways of AA metabolism, 10 microM eicosatetraynoic acid (ETYA), reduced the constrictor responses to all the concentrations of NA assayed. 2. The constrictor responses to NA were also reduced by the cyclooxygenase (COX) inhibitor, indomethacin (10 microM), as well as by the lipoxygenase inhibitor, nordihidroguaiaretic acid (1 microM; NDGA), whereas they were unmodified by the cytochrome P450 monooxigenase inhibitors, clotrimazole (10 microM), metyrapone (10 microM) and proadifen (10 microM). 3. The reduction in NA contractility induced by indomethacin was reverted with a decreasing order of potency by the thromboxane A2 analogue, U-46619 > prostaglandin (PG) E2 > PGF2alpha. The exposure of the mesenteric bed to NA increased the production of PGF2alpha, whereas it did not modify the production of the remaining AA metabolites. 4. The increase in the NA-induced contractions caused by endothelium removal, as well as by the inhibition of nitric oxide synthase (NOs) with NG-nitro-L-arginine methyl ester (400 microM; L-NAME), was suppressed by indomethacin but not by NDGA. These observations suggest that the lipoxygenase-derived metabolites are formed in the endothelium, whereas the COX-derived metabolites are formed in the vascular smooth muscle. 5. The TP receptor antagonist, SQ29548, did not modify the NA-induced contractions, either in the presence or in the absence of the endothelium. 6. Contractions elicited by KCI (60-100 mM) were unmodified by the AA metabolism inhibitors, ETYA, NDGA and indomethacin. 7. In summary, these results show that metabolites of AA, through both the COX and the lipoxygenase pathways, are involved in the NA-induced contractions in the rat mesenteric bed. The lipoxygenase metabolites are likely to be formed in the vascular endothelium, whereas the COX metabolite, which could be PGF2alpha, is apparently formed within the vascular smooth muscle.

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Section: Discussionsupporting

confidence: 92%

Effects of eicosanoids and nitric oxide on the noradrenaline‐induced contractions in the rat mesenteric bed

Peredo

Adler‐Graschinsky

2000

J. Autonom. Pharmacol.

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“…There have been many reports that NA stimulates the endothelium and then releases NO in various arterial preparations, as well as concomitantly modifying the response to NA 11,12 . In the present study, NA at concentrations of 0.001–1 µmol/L caused a concentration‐dependent contraction of the rat coronary artery and this contraction was markedly enhanced by l ‐NAME.…”

Section: Discussionsupporting

confidence: 53%

Involvement of Endothelial Cyclo‐oxygenase Metabolites in Noradrenaline‐induced Contraction of Rat Coronary Artery

Wang¹,

Nishihashi²,

Trandafir³

et al. 2005

Clin Exp Pharma Physio

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1. Noradrenaline (NA; 0.3 micromol/L) caused a contraction of the rat coronary artery that markedly increased in the presence of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME; 100 micromol/L) and arachidonic acid (1 micromol/L; P < 0.05). 2. The present experiments attempted to elucidate the endothelium dependency of the contraction and to pharmacologically characterize the factors involved in the contraction induced by NA (0.3 micromol/L) in the presence of L-NAME and arachidonic acid in ring preparations of the rat coronary artery. 3. The NA (0.3 micromol/L)-induced contraction was attenuated by a chemical remover of the endothelium (saponin at concentrations of 0.1 and 0.4 mg/mL) in a concentration-dependent manner (P < 0.05). 4. The cyclo-oxygenase (COX)-1 inhibitor flurbiprofen (0.01-1 micromol/L) and the COX-2 inhibitor nimesulide (0.01-1 micromol/L) attenuated the NA-induced contraction in a concentration-dependent manner and the inhibitory effect of flurbiprofen was significantly more potent than that of nimesulide (P < 0.05). The 5-lipoxigenase inhibitor ZM-230487 (1 micromol/L) did not affect the NA-induced contraction. 5. The thromboxane A2 (TXA2) synthetase inhibitor OKY-046 (30 micromol/L) and the TXA2 antagonist S-1452 (0.1-10 micromol/L) did not attenuate the NA-induced contraction. 6. These results indicate that the contraction induced by NA in the rat coronary artery in the presence of L-NAME and arachidonic acid is endothelium dependent and is due to endothelial COX metabolites of arachidonic acid.

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“…Kodama et al (1995), had reported an indomethacin-sensitive component in the constrictor properties of PGF 2a and U46619 in mesenteric microvessels of the rat. The contribution of COX-derived metabolites as modulators of the mouse mesenteric vascular tone remains, therefore, to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the non‐adrenergic/non‐cholinergic response to perivascular nerve stimulation in the double‐perfused mesenteric bed of the mouse

Legros

Tirapelli

Brochu

et al. 2007

British J Pharmacology

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Background and purpose: Calcitonin gene-related peptide (CGRP), a capsaicin-sensitive neuromodulator of splanchnic vascular tone in several animal species, remains poorly investigated in mouse models. We therefore assessed whether endogenous CGRP is a non-adrenergic/non-cholinergic (NANC) neuromodulator in the mesenteric vascular bed of the mouse. Experimental approach: Arterial and venous changes in perfusion pressure in response to perivascular nerve stimulation (PNS) were monitored in the mouse mesenteric bed under basal conditions or precontracted with KCl (artery) or U46619 (vein) in circuits pretreated with guanethidine, atropine, indomethacin and prazosin. Arterial responses to NANC were also characterized with a CGRP1 antagonist, haCGRP 8À37. Finally, the PNS-induced release of arterial CGRP was measured by enzyme immunoassay. Key results: HaCGRP 8À37 enhanced PNS-induced arterial increases in perfusion pressure under basal tone. PNS-induced stimulation of NANC triggered an haCGRP 8À37 or capsaicin-sensitive reduction in perfusion pressure of the pre-contracted arterial bed only. Chemical removal of the endothelium inhibited PNS-and haCGRP-induced reduction in perfusion pressure in the arterial mesenteric bed. Responses to NANC nerves were reduced by guanylate and adenylate cyclase inhibitors (1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one (ODQ)) and [9-(tetrahydro-2-furanyl)-9H-purin-6-amine] (SQ 22 536), respectively. A neuronal NOS inhibitor (7-nitroindazole; 7-NI) also enhanced the response to NANC in vessels from wild-type, eNOS KO but not iNOS KO mice. Finally, PNS enhanced the release of immunoreactive CGRP from the perfused arterial mesenteric bed. Conclusions and implications: Our study demonstrates a role for CGRP in the NANC-dependent reduction in perfusion pressure of the arterial but not venous mesenteric bed of the mouse. (2007) Keywords: CGRP; haCGRP 8À37 ; neuronal nitric oxide synthase; arterial mesenteric vasculature; mouse model British Journal of Pharmacology

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The Interaction between Endothelium-Derived Relaxing Factor (EDRF) and Eicosanoids in the Regulation of the Mesenteric Microcirculation

Cited by 8 publications

References 0 publications

Effects of eicosanoids and nitric oxide on the noradrenaline‐induced contractions in the rat mesenteric bed

Effects of eicosanoids and nitric oxide on the noradrenaline‐induced contractions in the rat mesenteric bed

Involvement of Endothelial Cyclo‐oxygenase Metabolites in Noradrenaline‐induced Contraction of Rat Coronary Artery

Characterization of the non‐adrenergic/non‐cholinergic response to perivascular nerve stimulation in the double‐perfused mesenteric bed of the mouse

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