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内皮素-1诱导的血管收缩仅由自发性高血压大鼠和Wistar Kyoto大鼠肠系膜小阻力动脉中的ET(A)受体介导。

The vasoconstriction induced by endothelin-1 is mediated only by ET(A) receptors in mesenteric small resistance arteries of spontaneously hypertensive rats and Wistar Kyoto rats.

作者信息

Rizzoni D, Porteri E, Piccoli A, Castellano M, Bettoni G, Pasini G, Agabiti-Rosei E

机构信息

Cattedra di Semeiotica e Metodologia Medica, U.O.P. Scienze Mediche, University of Brescia, Italy.

出版信息

J Hypertens. 1997 Dec;15(12 Pt 2):1653-7. doi: 10.1097/00004872-199715120-00068.

DOI:10.1097/00004872-199715120-00068
PMID:9488218
Abstract

OBJECTIVE

To evaluate the functional responses of mesenteric small resistance arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rat controls to endothelin-1 (ET-1), in the presence and absence of an ET(A) receptor antagonist drug as well as to an ET(B) receptor agonist.

METHODS

Twenty rats aged 12 weeks were studied. They were 10 SHR and 10 WKY rats. Mesenteric small resistance arteries (relaxed diameter 100-180 microm) were dissected and mounted on a micromyograph (Mulvany's technique). A dose-response curve for response to ET-1 was plotted for cumulative concentrations (from 10(-11) to 10(-8) mol/l) in the presence and absence of 10(-6) mol/l FR 139317 (a selective antagonist of ET(A) receptors). In addition, the effects of 10(-7) mol/l N-succinyl-[Glu9, Ala11,15]-endothelin 1 fragment 8-21 (IRL 1620, a selective agonist of ET(B) receptors) were evaluated.

RESULTS

The response of ET-1 was greater in WKY rats than it was in SHR. Almost all the vasoconstrictor effect of ET-1 could be prevented by addition of FR 139317, whereas the agonist of ET(B) receptors had no effect (no change in active force).

CONCLUSIONS

The contractile effects of ET-1 on mesenteric small resistance arteries of SHR and WKY rats are mediated mostly by ET(A) receptors, whereas ET(B) receptors play a minor role, if any. It is possible, however, that a vasoconstrictor effect of ET(B) receptors on the smooth muscle could be masked by the concomitant stimulation of endothelial ET(B) vasodilator receptors.

摘要

目的

评估自发性高血压大鼠(SHR)和Wistar-Kyoto(WKY)对照大鼠的肠系膜小阻力动脉在存在和不存在ET(A)受体拮抗剂药物的情况下对内皮素-1(ET-1)的功能反应,以及对ET(B)受体激动剂的反应。

方法

研究了20只12周龄的大鼠。其中10只为SHR大鼠,10只为WKY大鼠。解剖肠系膜小阻力动脉(舒张直径为100 - 180微米)并安装在微血管张力测定仪上(Mulvany技术)。绘制在存在和不存在10^(-6)摩尔/升FR 139317(一种ET(A)受体的选择性拮抗剂)的情况下,对ET-1累积浓度(从10^(-11)到10^(-8)摩尔/升)反应的剂量反应曲线。此外,评估了10^(-7)摩尔/升N-琥珀酰-[Glu9,Ala11,15]-内皮素1片段8 - 21(IRL 1620,一种ET(B)受体的选择性激动剂)的作用。

结果

ET-1在WKY大鼠中的反应比在SHR大鼠中更大。添加FR 139317几乎可以阻止ET-1的所有血管收缩作用,而ET(B)受体激动剂则没有作用(主动力无变化)。

结论

ET-1对SHR和WKY大鼠肠系膜小阻力动脉的收缩作用主要由ET(A)受体介导,而ET(B)受体即使有作用也很微小。然而,ET(B)受体对平滑肌的血管收缩作用可能会被内皮ET(B)血管舒张受体的同时刺激所掩盖。

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