INFLUENCE OF THE VASCULAR ENDOTHELIUM ON AGONIST-INDUCED CONTRACTIONS AND RELAXATIONS IN RAT AORTA
INFLUENCE OF THE VASCULAR ENDOTHELIUM ON AGONIST-INDUCED CONTRACTIONS AND RELAXATIONS IN RAT AORTA
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DOI：
10.1111/j.1476-5381.1986.tb11187.x
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发表时间：
1986-12-01
影响因子：
7.3
通讯作者：
WESTON, AH
中科院分区：
文献类型：
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作者：
BULLOCK, GR;TAYLOR, SG;WESTON, AH
用完整的大鼠主动脉段测量了血管内皮对激动剂诱导的收缩和舒张的影响。连续的摩擦段作为对照。血管紧张素II，组胺，去甲肾上腺素，U46619和uk14304收缩摩擦组织和完整组织。摩擦组织中这些激动剂的阈值致痉挛浓度低于完整制剂。摩擦后组织对血管紧张素II、组胺、去甲肾上腺素和UK14304的敏感性和反应性均高于完整组织。乙酰胆碱和组胺能缓解完整组织的痉挛，但对摩擦制剂没有作用。乙酰胆碱的松弛作用通过与血红蛋白的预孵育而消除。在哌唑嗪、去甲肾上腺素或uk14304的存在下，使完整组织的既定收缩松弛。这些作用可由咪唑嗪或与血红蛋白预孵育拮抗。在完整的制剂中，咪唑嗪对uk14304的致痉挛敏感性和反应性没有影响。血红蛋白预处理增强了去甲肾上腺素、U46619或uk14304在完整组织中的致痉挛作用，但在摩擦制剂中对这些反应没有影响。环GMP在完整组织中的浓度高于摩擦组织。乙酰胆碱浓度(10 μ。M)在完整的制剂中，引起最大的机械抑制会显著增加环GMP浓度。然而，UK 14304 （10 .mu）未产生可检测到的环GMP浓度变化。M)或乙酰胆碱（10 nM），这两种浓度对抑制机械活性同样有效。当去甲肾上腺素的阈值浓度存在时，血管紧张素II的收缩作用增强，与摩擦制剂中观察到的收缩作用相当。在去甲肾上腺素浓度较高的情况下，血管紧张素II总是产生额外的收缩。由此可见，血管内皮的存在限制了多种激动剂的致痉挛作用。虽然像去甲肾上腺素和uk14304这样的痉挛素可以通过α刺激内皮源性放松因子（EDRF）的释放。2-肾上腺素受体，EDRF的抑制作用主要是由于这种物质的自发释放。
The influence of the vascular endothelium on agonist-induced contractions and relaxations has been measured using intact segments of rat aorta. Contiguous rubbed segments were used as controls. Angiotensin II, histamine, noradrenaline, U46619 and UK 14304 contracted both rubbed and intact tissues. The threshold spasmogenic concentrations of these agonists were lower in rubbed tissues than in intact preparations. The sensitivity and responsiveness of tissues to angiotensin II, histamine, noradrenaline and UK14304 were greater in rubbed than in intact tissues. Acetylcholine and histamine relaxed the established spasms of intact tissues but not those of rubbed preparations. These relaxant effects of acetylcholine were abolished by pre-incubation with haemoglobin. In the presence of prazosin, noradrenaline or UK 14304 relaxed established contractions in intact tissues. These effects were antagonized by idazoxan or by pre-incubation with haemoglobin. In intact preparations, idazoxan had no effect on the spasmogenic sensitivity and responsiveness to UK 14304. Pre-incubation with haemoglobin augmented the spasmogenic actions of noradrenaline, U46619 or UK 14304 in intact tissues, but had no effect on these responses in rubbed preparations. Tissue concentrations of cyclic GMP were greater in intact than in rubbed tissues. A concentration of acetylcholine (10 .mu.M) evoking just maximal mechanical inhibition produced a significant increase in cyclic GMP concentration in intact preparations. However, no detectable changes in cyclic GMP concentration were produced by UK 14304 (10 .mu.M) or by acetylcholine (10 nM), concentrations which were equi-effective in inhibiting mechanical activity. In the presence of threshold spasmogenic concentrations of noradrenaline, the contractile effects of angiotensin II were augmented and became comparable to those observed in rubbed preparations. In the presence of greater concentrations of noradrenaline, angiotensin II always produced an additional contraction. It is concluded that the presence of the vascular endothelium limits the spasmogenic action of a variety of agonists. Although spasmogens like noradrenaline and UK 14304 can stimulate the release of endothelium-derived relaxing factor (EDRF) via .alpha.2-adrenoceptors, the inhibitory effects of EDRF largely result from the spontaneous release of this substance.