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|Type:||Artigo de periódico|
|Title:||CHARACTERIZATION OF FUNCTIONAL ENDOTHELIN RECEPTORS IN THE CANINE ISOLATED-PERFUSED SPLEEN|
|Abstract:||The endothelin receptor subtypes involved in the vasoconstriction, capsular smooth muscle contraction, prostaglandin E(2) and prostacyclin release induced by endothelin-l have been investigated in the canine isolated perfused spleen using both the endothelin ET(A) receptor antagonist FR 139317 and the endothelin ET(B) receptor agonist IRL 1620. The isolated canine spleen was perfused with warmed (37 degrees C) and oxygenated (95% O-2/5% CO2) Krebs solution at constant now with continuous recording of splenic arterial perfusion pressure and spleen weight, Samples of splenic venous effluent were collected to determine the amounts of prostaglandin E(2) and prostacyclin, measured by radioimmunoassay. Endothelin-1 (4-200 mu mol) and IRL 1620 (20-1000 pmol) dose-dependently increased splenic arterial perfusion pressure but the former was more potent on a molar basis (the molar dose ratio IRL/endothelin-1 required to increase splenic arterial vascular resistance by 25% was approximately 33). The infusion of the nitric oxide inibitor N-omega-nitro-L-arginine methyl ester (10 mu M), but not of the enantiomer N-omega-nitro-D-arginine methyl ester, significantly potentiated the increase in splenic arterial vascular resistance induced by endothelin-1. The infusion of FR 139317 (1 mu M) markedly attenuated the increased splenic arterial perfusion pressure induced by endothelin-1 without affecting that evoked by IRL 1620. At the highest dose (200 pmol, endothelin-1 induced a small but significant capsule contraction as reflected by the reduction in the spleen weight. The infusion of FR 139317 (1 mu M) abolished this contractile effect. IRL 1620 (in doses up to 1000 pmol) did not significantly affect the capsule tone. The administration of either endothelin-1 (20-200 pmol) or IRL 1620 (20-1000 pmol) caused the release of 6-oxo-prostaglandin F-1 alpha (breakdown product of prostacyclin) and prostaglandin E(2) into the splenic venous effluent. The amount of both prostanoids released by endothelin-1 was significantly greater than that induced by IRL 1620. FR 139317 (1 mu M) significantly reduced (P < 0.05) the release of both 6-oxo-prostaglandin F-1 alpha and prostaglandin E(2) by endothelin-1 without affecting that released by IRL 1620. The results demonstrate that the release of prostaglandins and nitric oxide modulates the vasoconstrictor activity of endothelin-1 in the splenic circulation. Furthermore, the vasoconstriction and eicosanoids (prostacyclin and prostaglandin E(2)) release by endothelin-1 are due to activation of both endothelin ET(A) and ET(B) receptors, although the former seems to be the predominant form. The splenic capsule contraction is mediated by activation of endothelin ET(A) receptors only.|
NITRIC OXIDE (NO)
|Editor:||Elsevier Science Bv|
|Appears in Collections:||Unicamp - Artigos e Outros Documentos|
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