Sun M H, Ishine T, Lee T J
Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62794-1222, USA.
Eur J Pharmacol. 1997 Sep 10;334(2-3):165-71. doi: 10.1016/s0014-2999(97)01166-7.
Dopamine has been shown to induce pial arterial relaxation and constriction in several species. Its mode of action on pial veins, however, remains unclarified. The vasomotor effect of dopamine on porcine pial veins was, therefore, examined using an in vitro tissue bath technique. The results indicated that dopamine constricted exclusively isolated ring segments of pial veins in the presence or absence of active muscle tone. The constriction induced by dopamine was not affected by N(omega)-nitro-L-arginine (L-NNA, 2 x 10(-5) M) or indomethacin (10(-5) M). Only in few preparations was the constriction induced by maximum concentration of dopamine potentiated by L-NNA, suggesting that dopamine at high concentrations may release NO or a NO-related substance. In the presence of L-NNA (2 x 10(-5) M), dopamine-induced constriction was inhibited by phentolamine and yohimbine (but not prazosin) in a concentration-dependent manner with maximum inhibition at 10(-6) M. SKF38393 and 6-bromo-APB (selective dopamine D1 receptor agonists) and LY171555 (a selective dopamine D2 receptor agonist) also induced pial venous constriction exclusively in the presence of L-NNA. The constriction was not affected by phentolamine (10(-6) M). The order of potency for these agonists in the presence of phentolamine, propranolol, guanethidine and L-NNA was: 6-bromo-APB > SKF38393 > dopamine > LY171555. The dopamine-induced constriction in the presence of phentolamine was further inhibited by both SCH23390 (a selective dopamine D1 receptor antagonist) and sulpiride (a selective dopamine D2 receptor antagonist), but was not affected by dopamine D3 or D4 receptor antagonists. These results indicate that dopamine at low and high concentrations induces exclusively constriction of isolated porcine pial veins. The constriction is mediated by postsynaptic alpha2-adrenoceptors, and dopamine D1 and D2 receptors.
多巴胺已被证明可在多个物种中诱导软脑膜动脉舒张和收缩。然而，其对软脑膜静脉的作用方式仍不明确。因此，使用体外组织浴技术研究了多巴胺对猪软脑膜静脉的血管舒缩作用。结果表明，无论有无主动肌张力，多巴胺均可使分离出的软脑膜静脉环段单独收缩。多巴胺诱导的收缩不受N（ω）-硝基-L-精氨酸（L-NNA，2×10⁻⁵ M）或吲哚美辛（10⁻⁵ M）的影响。仅在少数制剂中，L-NNA可增强最大浓度多巴胺诱导的收缩，提示高浓度多巴胺可能释放一氧化氮（NO）或与NO相关的物质。在L-NNA（2×10⁻⁵ M）存在的情况下，酚妥拉明和育亨宾（而非哌唑嗪）以浓度依赖方式抑制多巴胺诱导的收缩，在10⁻⁶ M时抑制作用最大。SKF38393和6-溴-APB（选择性多巴胺D1受体激动剂）以及LY171555（选择性多巴胺D2受体激动剂）也仅在L-NNA存在时诱导软脑膜静脉收缩。该收缩不受酚妥拉明（10⁻⁶ M）的影响。在酚妥拉明、普萘洛尔、胍乙啶和L-NNA存在的情况下，这些激动剂的效力顺序为：6-溴-APB＞SKF38393＞多巴胺＞LY171555。在酚妥拉明存在的情况下，多巴胺诱导的收缩进一步受到SCH23390（选择性多巴胺D1受体拮抗剂）和舒必利（选择性多巴胺D2受体拮抗剂）的抑制，但不受多巴胺D3或D4受体拮抗剂的影响。这些结果表明，低浓度和高浓度的多巴胺均可使分离出的猪软脑膜静脉单独收缩。该收缩由突触后α2-肾上腺素能受体、多巴胺D1和D2受体介导。
