Participação da via do óxido nítrico na resposta relaxante induzida por E- cinamaldeído-oxima em artéria mesentérica superior isolada de rato.

Abstract

Decreased availability of NO in the vasculature promotes the progression of cardiovascular diseases and oximes represents a NO-donor group capable of to restore this defictIn rat superior mesenteric arterial rings, as non-aromatic oximes: diacetylmonoxime and dimetylglycone-oxime, as aromatic oximes: benzofenone-oxime, 4-Cl-benzofenone and cinnamaldheyde-oxime isomeric mixture were markedly less potent than tans-E-cinnamaldheyde-oxime (E CAOx) whose relaxation was concentration-dependent in denuded-endothelum pre-contracted rings with PHE (pD2 = 5,11 ± 0,05), or U46619 (pD2 = 5,03 ± 0,06), an tromboxanic agonist TP, or with A23187 (pD2 = 4,70 ± 0,06), an Ca2+ ionophore, beyond KCl 60mM (pD2 = 4,50 ± 0,06). The relaxation was not modified by endothelium or L-NAME (100 μM, NOS inhibitor), proadifen (30 M; inibidor do citocromos P450), ou de N-acetyl-L-Cysteyn (1 mM e 3 mM; an NO- scavenger). However, was affected by cytochromos P4501A1 and NADPH-dependent reductases inhibitor, 7ethoxyresorufin (7 ER, 10 μM; pD2 = 4,82 ± 0,07), and NO scavenger, PTIO (300 M; pD2 = 4,68 ± 0,11). Demonstrating that E-CAOx induces independent-endothelium relaxation with a possible NO production, mediated by NADPH-dependent reductases. These results corroborate with E-CAOx action of to increase DAF-T fluorescence, in rat aorta smooth miocytes, abolished by 7-ER pre-incubation. Futhermore, the Emax decrease caused by (Rp)-8pCPT-cGMPS (10 M; PKG inhibitor), plus potency reduction by ODQ presence (0,1 M; pD2 = 4,65 ± 0,07 e 10 M; pD2 = 4,41 ± 0,04), a soluble guanylyl-cyclase inhibitor, reforce the pathway NO/cGC/cGMP/PKG participation. On the other hand, the presences of KCl 20mM and TEA (1 mM; pD2 = 4,62 ± 0,04), a BKCa blocker, were capable of the interfering in response, but not 4-AP (1 mM; Kv blocker) and Glibenclamide (10 M; a KATP blocker). In ODQ (10 M) combinations, only KCl 20mM, interpose on Emax, suggesting that K+ channels contribution, majorly BKCa, is sGC-activation dependent. Due relaxing pre-contracted rings: with S(-)BayK 8644 (pD2 = 4,95 ± 0,05), a direct activator of dihydropiridine-sensitive Cav, and rings pre-contracted with PHE in the presence of Niphedipine (1 M), E-CAOx can also to be acting by inhibits Ca2+ influx through dihydropiridine-sensitive Cav or to interfere in contract mechanisms ulterior to Ca2+ entry, as is the case of Na+/Ca2+ exchanger. This hypothesis is justified by reduction in response due the Ni+2 presence (Na+/Ca2+ inhibitor). In conclusion, the data shown that E-CAOx was the more potent oxime investigated with NO production thougth NADPH-dependent reductases action and subsequentely pathway CGs/GMPc/PKG activation associated to BKCa activation, Cav inhibition and exchalenger Na+/Ca2+activation.