Sunano S, Nakahira T, Kawata K, Sekiguchi F
Department of Anatomy and Physiology, Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Eur J Pharmacol. 2001 Jun 29;423(1):47-55. doi: 10.1016/s0014-2999(01)01081-0.
The time course of the response to prolonged application of acetylcholine in mesenteric arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) was compared. Only a relaxing response, which was blocked by N(omega)-nitro-L-arginine (L-NOARG), was observed after the prolonged application of a low concentration of acetylcholine (10(-8) M) in both preparations; the response was impaired in SHRSP preparations. Prolonged application of a high concentration of acetylcholine (10(-5) M) induced a second contractile response after a first relaxing response in SHRSP preparations under basal conditions and in WKY preparations in the presence of L-NOARG. This contractile response was attenuated by indomethacin. In the presence of a combination of apamin and charybdotoxin, the relaxing response to the high concentration of acetylcholine was reduced and a contractile response, which was abolished by indomethacin, appeared. In the presence of all of these blockers, a contractile response, which was blocked by cyclo(D-alpha-aspartyl-L-propyl-D-valyl-L-leucyl-D-tryptophyl) (BQ-123), was observed in preparations from WKY but not in preparations from SHRSP. Results indicate that prolonged application of acetylcholine in rat mesenteric arteries induces the release of endothelium-derived relaxing, contracting, hyperpolarizing factors and endothelin-1, and that the mode of action differs between preparations from WKY and SHRSP.
比较了易中风自发性高血压大鼠（SHRSP）和Wistar Kyoto大鼠（WKY）肠系膜动脉中长时间应用乙酰胆碱后的反应时程。在两种制剂中长时间应用低浓度乙酰胆碱（10⁻⁸M）后，仅观察到一种舒张反应，该反应可被N（ω）-硝基-L-精氨酸（L-NOARG）阻断；SHRSP制剂中的反应受损。在基础条件下，长时间应用高浓度乙酰胆碱（10⁻⁵M）会在SHRSP制剂中以及在L-NOARG存在下的WKY制剂中，在首次舒张反应后诱导出第二次收缩反应。这种收缩反应被吲哚美辛减弱。在蜂毒明肽和大蝎毒素联合存在的情况下，对高浓度乙酰胆碱的舒张反应降低，并且出现了一种可被吲哚美辛消除的收缩反应。在所有这些阻滞剂存在的情况下，在WKY的制剂中观察到一种可被环（D-α-天冬氨酰-L-丙氨酰-D-缬氨酰-L-亮氨酰-D-色氨酰）（BQ-123）阻断的收缩反应，但在SHRSP的制剂中未观察到。结果表明，在大鼠肠系膜动脉中长时间应用乙酰胆碱会诱导内皮源性舒张因子、收缩因子、超极化因子和内皮素-1的释放，并且WKY和SHRSP的制剂之间作用方式不同。
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