Criddle David Neil, Madeira Socorro Vanesca Frota, Soares de Moura Roberto
Laboratório de Farmacologia dos Canais Iônicos, Departamento de Ciências Fisiológicas, CCS, Universidade Estadual do Ceará, Av. Paranjana 1700, Fortaleza CE 60740-000, Brazil.
J Pharm Pharmacol. 2003 Mar;55(3):359-65. doi: 10.1211/002235702694.
The possible involvement of the endothelium in the vasodilator action of eugenol was investigated in the mesenteric vascular bed (MVB) of the rat. Bolus injections of eugenol (0.2, 2 and 20 micromol) and acetylcholine (ACh; 10, 30 and 100 pmol) induced dose-dependent vasodilator responses in noradrenaline-precontracted beds that were partially inhibited by pretreatment of the MVB with deoxycholate (1 mg mL(-1)) to remove the endothelium (approximately 14% and approximately 30% of the control response remaining at the lowest doses of ACh and eugenol, respectively). The vasodilator effect of glyceryl trinitrate (1 micromol) was unaltered by deoxycholate. In the presence of either N(omega)-nitro-L-arginine methyl ester (300 microM) or tetraethylammonium (1 mM)the response to ACh was partially reduced, whereas eugenol-induced vasodilation was unaffected. Similarly the vasodilator effect of eugenol was not inhibited by indometacin (3 microM). Under calcium-free conditions the vasoconstrictor response elicited by bolus injections of noradrenaline (10 nmol) was dose-dependently and completely inhibited by eugenol (0.1-1 mM). Additionally, the pressor effects of bolus injections of calcium chloride in potassium-depolarized MVBs were greatly reduced in the presence of eugenol (0.1 mM), with a maximal reduction of approximately 71% of the control response. Our data showed that eugenol induced dose-dependent, reversible vasodilator responses in the rat MVB, that were partially dependent on the endothelium, although apparently independent of nitric oxide, endothelium-derived hyperpolarizing factor or prostacyclin. Furthermore, an endothelium-independent intracellular site of action seemed likely to participate in its smooth muscle relaxant properties.
在大鼠肠系膜血管床（MVB）中研究了内皮细胞在丁香酚血管舒张作用中的可能参与情况。在去甲肾上腺素预收缩的血管床中，推注丁香酚（0.2、2和20微摩尔）和乙酰胆碱（ACh；10、30和100皮摩尔）可诱导剂量依赖性血管舒张反应，用脱氧胆酸盐（1毫克/毫升）预处理MVB以去除内皮细胞后，这些反应会部分受到抑制（在ACh和丁香酚的最低剂量下，分别约有14%和约30%的对照反应保留）。硝酸甘油（1微摩尔）的血管舒张作用不受脱氧胆酸盐影响。在存在N（ω）-硝基-L-精氨酸甲酯（300微摩尔）或四乙铵（1毫摩尔）的情况下，对ACh的反应会部分降低，而丁香酚诱导的血管舒张不受影响。同样，吲哚美辛（3微摩尔）也不抑制丁香酚的血管舒张作用。在无钙条件下，推注去甲肾上腺素（10纳摩尔）引起的血管收缩反应被丁香酚（0.1 - 1毫摩尔）剂量依赖性且完全抑制。此外，在存在丁香酚（0.1毫摩尔）的情况下，在钾去极化的MVB中推注氯化钙的升压作用大大降低，最大降低约为对照反应的71%。我们的数据表明，丁香酚在大鼠MVB中诱导剂量依赖性、可逆的血管舒张反应，这些反应部分依赖于内皮细胞，尽管显然独立于一氧化氮、内皮衍生的超极化因子或前列环素。此外，一个不依赖内皮细胞的细胞内作用位点似乎可能参与其平滑肌舒张特性。
