Endothelium-dependent contractions to NG-nitro-L-arginine methyl ester in the porcine isolated splenic artery are sensitive to cyclooxygenase and lipoxygenase inhibitors

Lot, T. Y.; Stärk, Gerhard; Wilson, V.G.

doi:10.1007/bf00168782

Cited by 20 publications

(9 citation statements)

References 13 publications

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“…In the porcine pulmonary artery,¯urbiprofen inhibited both U46619-and L-NAMEinduced contractions. The latter observation is similar to those reported in both the splenic (Lot et al, 1993) and coronary (Nakaike et al, 1995) arteries of the pig, and indicates the involvement of a vasoconstrictor prostanoid. In the human pulmonary artery, however,¯urbiprofen increased U46619induced tone and produced a contraction in the presence of L-NAME (data not shown).…”

Section: The Role Of Nitric Oxide and Prostanoids At Restsupporting

confidence: 89%

“…Pulmonary arteries were located running next to bronchial airways, and carefully followed, cutting away any branches. The arteries were placed in 20 ml of K‐H Solution containing 2% ficoll, which had previously been gassed for 5–10 min with 95% O 2 :5% CO 2 , and stored overnight at 4°C; ficoll was used to prevent osmotic swelling of the cells (Lot et al , 1993).…”

Section: Methodsmentioning

confidence: 99%

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Differential role of vasoactive prostanoids in porcine and human isolated pulmonary arteries in response to endothelium‐dependent relaxants

Lawrence

Clelland

Beggs

et al. 1998

British J Pharmacology

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1 The pig is increasingly being used in medical research, both as a model of the human cardiovascular system, and as a possible source of organs for xenotransplantation. However, little is known about the comparative functions of the vascular endothelium between porcine and human arteries. We have therefore compared the e ects of two endothelium-dependent vasorelaxants, acetylcholine (ACh) and the Ca 2+ -ATPase inhibitor, cyclopiazonic acid (CPA) on the porcine and human isolated pulmonary artery using isometric tension recording. 2 ACh and CPA produced endothelium-dependent relaxations of both the human and porcine pulmonary arteries. 3 In the porcine pulmonary artery, the cyclo-oxygenase inhibitor,¯urbiprofen had no e ect on relaxations to ACh (E max : control 67.8+8.8% versus 72.4+9.5% (n=11)) or CPA (E max : control 79.6+5.0% versus 94.0+10.6% (n=7)). The nitric oxide synthase inhibitor, L-NAME converted relaxations to both ACh and CPA into contractile responses (maximum response: ACh 30.0+11.1% (n=10); CPA 80.4+26.2% (n=8) of U46619-induced tone). These contractile responses in the presence of L-NAME were abolished by¯urbiprofen. 4 In the human pulmonary artery, L-NAME and¯urbiprofen partly attenuated relaxations to ACh (E max : control: 45.1+12.1%;¯urbiprofen: 33.4+13.5%; L-NAME: 10.1+7.2%) and CPA (E max : control: 78.1+5.5%;¯urbiprofen: 69.6+7.2%; L-NAME 37.9+10.7% of U46619-induced tone). These responses were abolished by the combination of both inhibitors. 5 We have demonstrated that while the release of nitric oxide is important in responses to endotheliumdependent vasorelaxants in both human and porcine pulmonary arteries, in the human arteries, there is an important role for vasorelaxant prostanoids whilst in the porcine arteries, vasoconstrictor prostanoids are released.

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Section: The Role Of Nitric Oxide and Prostanoids At Restsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Differential role of vasoactive prostanoids in porcine and human isolated pulmonary arteries in response to endothelium‐dependent relaxants

Lawrence

Clelland

Beggs

et al. 1998

British J Pharmacology

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“…Such contractile activity is known to occur also in precontracted endotheliumcontaining rings of rat aorta exposed to DCLHb, but to be negligible or absent in such tissues when the basal tone is not first increased by a vasoconstrictor (Muldoon et al 1996). Other evidence suggests that endothelium-derived vasoconstrictor metabolites of arachidonic acid may also participate in the vasoconstrictor effect of Hb (Lot and Wilson 1993). Additional mechanisms through which DCLHb may, at least theoretically, cause a vasoconstrictor effect in isolated blood vessels include the generation of reactive oxygen species secondary to the autooxidation or chemically induced oxidation of DCLHb (Bunn and Forget 1986), the release of endothelin from endothelial cells (Schultz et al 1993;Gulati et al 1995), or direct interaction with drug receptors commonly found in vascular smooth muscle (e.g., α-adrenoceptors, angiotensin receptors, etc.).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of the contractile effect of diaspirin-cross-linked hemoglobin in rat isolated aorta strip denuded of endothelium as revealed using an oil-immersion procedure

Rioux

Drapeau²,

Audet³

et al. 1996

Can. J. Physiol. Pharmacol.

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Diaspirin-cross-linked hemoglobin (DCLHb) is a chemically modified hemoglobin (Hb) (i.e., alpha-subunits are cross-linked by a covalent bond) currently being tested as a potential oxygen-carrying blood substitute. It was examined for possible vasoactive properties, using the rat isolated aorta strip denuded of endothelium. In this experimental model, DCLHb (1.6-155 microM) was found to be inactive as a vasoconstrictor when added to the Krebs medium but to elicit contractile responses once the Krebs medium containing DCLHb was replaced by mineral oil, a procedure that favors the sequestration of a fixed amount of DCLHb within a substantially reduced volume of extracellular fluid. The contractile activity of DCLHb in our experimental model (i.e., prior exposure of tissues to drugs in the Krebs medium followed by replacement of the Krebs medium by mineral oil) was mimicked by methemoglobin and metmyoglobin, but not by cytochrome c, albumin, hemin, hematin, Fe2+, and a variety of hemorphins. It was abolished by indomethacin, SQ-29548 (prostaglandin H2-thromboxane A2 receptor antagonist), thiourea, or N-2-mercaptopropionylglycine (MCPG), reduced partially by verapamil, but not affected by dazmegrel, MK-886 (leukotriene biosynthesis inhibitor), dimethylsulfoxide, vitamin C or E, deferoxamine, NG-nitro-L-arginine, naloxone, and a variety of other drug receptor antagonists (e.g., prazosin) and protease inhibitors (e.g., pepstatin). Rat aorta strips denuded of endothelium exhibited contractile responses to arachidonic acid added in the Krebs medium (i.e., with no mineral oil added afterwards). Such contractile activity was reduced by SQ-29548, thiourea, or MCPG. Addition of U-46619 (prostaglandin H2-thromboxane A2 mimetic) to the Krebs medium also elicited contractile responses in rat aorta strips denuded of endothelium. Such contractile activity was reduced by SQ-29548, thiourea, or verapamil but not by MCPG. Within the limitations of our experimental approach, these results suggest that (1) the contractile activity of DCLHb in rat aorta strips denuded of endothelium following replacement of the Krebs medium by mineral oil involves the participation of a secondary mediator, which could be a vasoconstrictor metabolite of arachidonic acid; (2) the participation of reactive oxygen species, potential degradation products of DCLHb (e.g., heme, Fe2+, hemorphins), or other mediators in the contractile activity of DCLHb is unlikely; and (3) Ca2+ entry into target cells might be involved in the process by which DCLHb elicits its contractile activity in our experimental model.

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“…Receptormediated release of endothelium-derived relaxing factor and PGI 2 are coupled in bovine aortic endothelial cells (BAEC), and several agonists produce vasodilatation through the simultaneous release of NO and PGI 2 (6,14). Radicicol has been shown to inhibit COX-2 expression in smooth muscle cells (5).…”

Section: Role Of the Cox Pathway And Superoxide On The Inhibition Of mentioning

confidence: 99%

Effects of hsp90 binding inhibitors on sGC-mediated vascular relaxation

Yetik‐Anacak

Xia

Dimitropoulou

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Vascular soluble guanylate cyclase (sGC) exists in multimeric complexes with endothelial nitric oxide (NO) synthase (eNOS) and heat shock protein 90 (hsp90). Whereas disruption of hsp90-eNOS complexes clearly attenuates eNOS-dependent vascular relaxation, the contribution of sGC-hsp90 complexes to eNOS- or NO donor-dependent relaxations remains unclear. Isolated rat thoracic aortic rings were preincubated with structurally diverse hsp90 binding inhibitors, radicicol (RA) or geldanamycin (GA), or vehicle for 0.5, 1, or 15 h. Preconstricted vessels were exposed to ACh, 8-bromo-cGMP (8-BrcGMP), forskolin, or one of three NO donors: nitroglycerin (NTG), sodium nitroprusside, or spermine NONOate (SNN). Both RA and GA inhibited endothelium-dependent relaxations dose dependently. Indomethacin or the antioxidant tiron did not affect the inhibition of ACh-induced relaxations by GA. Long-term (15 h) exposure to RA inhibited all NO donor-induced relaxations; however, GA inhibited SNN-induced relaxation only. The effects of GA and RA appeared to be selective because 15-h treatment with either agent did not affect forskolin-induced relaxations and only slightly decreased 8-BrcGMP-induced relaxations. Similarly to their effects on NO-donor-induced relaxation, 15-h exposure to RA, but not to GA, decreased hsp90-bound sGC protein expression and NTG-stimulated cGMP formation in aortic rings, whereas RA more than GA reduced SNN-stimulated cGMP formation. We conclude that RA, much more so than GA, selectively inhibits sGC-dependent relaxations of aortic rings by reducing sGC expression, disrupting sGC-hsp90 complex formation and decreasing cGMP formation. These studies suggest that hsp90 regulates both eNOS- and sGC-dependent relaxations.

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Endothelium-dependent contractions to NG-nitro-L-arginine methyl ester in the porcine isolated splenic artery are sensitive to cyclooxygenase and lipoxygenase inhibitors

Cited by 20 publications

References 13 publications

Differential role of vasoactive prostanoids in porcine and human isolated pulmonary arteries in response to endothelium‐dependent relaxants

Differential role of vasoactive prostanoids in porcine and human isolated pulmonary arteries in response to endothelium‐dependent relaxants

Mechanism of the contractile effect of diaspirin-cross-linked hemoglobin in rat isolated aorta strip denuded of endothelium as revealed using an oil-immersion procedure

Effects of hsp90 binding inhibitors on sGC-mediated vascular relaxation

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