Hendriks M G, Pfaffendorf M, van Zwieten P A
Department of Pharmacotherapy, Academic Medical Centre, Amsterdam, The Netherlands.
Blood Press. 1993 Dec;2(4):332-8. doi: 10.3109/08037059309077176.
Possible hypertension-related alterations in the nature- and receptor reserve of the muscarinic (M) receptors mediating endothelium-dependent vasodilation remain to be elucidated. Therefore we used 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine (4-DAMPmustard), an irreversible M3-receptor antagonist, to estimate the receptor reserve for the methacholine (MCh)-induced endothelium-dependent vasodilation in perfused mesenteric vascular bed preparations obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) rats, respectively. The concentration-response curve parameters for the MCh-induced vasodilation were similar in both types of preparations. 4-DAMPmustard concentration-dependently decreased the maximal effect (Emax) of MCh without altering (N.S.) the pD2 in either type of preparation. The Emax was decreased to the same extent (N.S.) in both types of preparations. The dissociation constants of MCh for the response to muscarinic stimulation were comparable in preparations from SHR and WKY rats. The receptor reserve for this response, which is relatively low, does not appear to differ between vessels from SHR and WKY. It is concluded that an endothelial dysfunction does not seem to occur in perfused mesenteric resistance vessels from SHR. Also, the nature- and M-receptor reserves to not appear to differ. Therefore there are no important hypertension-related alterations in the M-receptor mediating endothelium-dependent vasodilation, at least in the experimental model used.
介导内皮依赖性血管舒张的毒蕈碱（M）受体在性质和受体储备方面可能与高血压相关的改变仍有待阐明。因此，我们使用4-二苯基乙酰氧基-N-（2-氯乙基）-哌啶（4-DAMP芥末），一种不可逆的M3受体拮抗剂，分别评估从自发性高血压大鼠（SHR）和Wistar-Kyoto大鼠（WKY）获得的灌注肠系膜血管床制剂中，乙酰甲胆碱（MCh）诱导的内皮依赖性血管舒张的受体储备。两种制剂中MCh诱导的血管舒张的浓度-反应曲线参数相似。4-DAMP芥末浓度依赖性地降低了MCh的最大效应（Emax），而在两种制剂中均未改变（无统计学差异）pD2。两种制剂中的Emax降低到相同程度（无统计学差异）。SHR和WKY大鼠制剂中MCh对毒蕈碱刺激反应的解离常数相当。这种反应的受体储备相对较低，SHR和WKY大鼠的血管之间似乎没有差异。得出的结论是，SHR灌注的肠系膜阻力血管似乎未发生内皮功能障碍。此外，性质和M受体储备似乎没有差异。因此，至少在所使用的实验模型中，介导内皮依赖性血管舒张的M受体没有重要的与高血压相关的改变。
