ENDOTHELIUM-DERIVED CONTRACTING FACTORS IN RESISTANCE ARTERIES OF YOUNG SPONTANEOUSLY HYPERTENSIVE RATS BEFORE DEVELOPMENT OF OVERT HYPERTENSION
ENDOTHELIUM-DERIVED CONTRACTING FACTORS IN RESISTANCE ARTERIES OF YOUNG SPONTANEOUSLY HYPERTENSIVE RATS BEFORE DEVELOPMENT OF OVERT HYPERTENSION
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DOI：
10.1161/01.hyp.21.3.280
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发表时间：
1993-03-01
期刊：
影响因子：
8.3
通讯作者：
DIEDERICH, D
中科院分区：
文献类型：
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作者：
JAMESON, M;DAI, FX;DIEDERICH, D
由于内皮衍生的环氧合酶依赖性收缩因子的产生增加，成年自发性高血压大鼠（SHR）的血管舒张受到损害。为了验证 SHR 中内皮功能的改变先于并导致显性高血压发生的假设，我们在肌动描记图中比较了 4 周龄 SHR 和 Wistar-Kyoto (WKY) 大鼠的内皮介导的肠系膜阻力动脉松弛。乙酰胆碱（10（-9）至10（-4）M）在用去甲肾上腺素预收缩（ED50）的SHR和WKY动脉中引起类似的松弛。在从 SHR 获得的动脉中，而不是从 WKY 大鼠获得的动脉中，舒张被更高浓度的乙酰胆碱（10(-6) 至 10(-5) M）的收缩反应所取代。收缩反应是内皮依赖性的，被硝基L-精氨酸（10(-4) M）增强，并通过用吲哚美辛（10(-5) M）或3-氨基-1,2,4-三唑（10(-3) M）（一种通过环氧合酶途径产生超氧阴离子的抑制剂）预处理来预防。抑制血栓素合成酶(CGS-13080, 5 x 10(-5) M)和拮抗前列腺素H2/血栓素A2受体(SQ-29,548, 5 x 10(-5) M)未能阻断SHR动脉中乙酰胆碱的收缩反应。 16 周龄 SHR 大鼠的肠系膜动脉中乙酰胆碱介导的舒张作用显着受损，但 WKY 大鼠则没有。在所有年龄段的 SHR 和 WKY 大鼠的动脉中，硝普钠产生的不依赖于内皮的舒张以及对去甲肾上腺素和内皮素的收缩反应是相当的。总之，“高血压前期”SHR 大鼠肠系膜动脉的内皮依赖性松弛因似乎是超氧阴离子的收缩因子的产生而受到损害。
Vascular relaxations are impaired in adult spontaneously hypertensive rats (SHRs) because of increased production of an endothelium-derived, cyclooxygenase-dependent contractile factor or factors. To test the hypothesis that alterations in endothelial function precede and contribute to the development of overt hypertension in SHRs, we compared in myographs endothelium-mediated relaxations of mesenteric resistance arteries from 4-week-old SHRs and Wistar-Kyoto (WKY) rats. Acetylcholine (10(-9) to 10(-4) M) induced comparable relaxations in SHR and WKY arteries precontracted (ED50) with norepinephrine. In arteries obtained from SHRs but not from WKY rats, relaxations were replaced by contractile responses with higher concentrations of acetylcholine (10(-6) to 10(-5) M). The contractile responses were endothelium dependent, were augmented by nitro L-arginine (10(-4) M), and were prevented by pretreatment with indomethacin (10(-5) M) or 3-amino-1,2,4-triazole (10(-3) M), an inhibitor of superoxide anion production via the cyclooxygenase pathway. Inhibition of thromboxane synthetase (CGS-13080, 5 x 10(-5) M) and antagonism of prostaglandin H2/thromboxane A2 receptors (SQ-29,548, 5 x 10(-5) M) failed to block the contractile response to acetylcholine in SHR arteries. Acetylcholine-mediated relaxations were significantly impaired in mesenteric arteries from 16-week-old SHRs but not from WKY rats. Endothelium-independent relaxations produced by sodium nitroprusside and contractile responses to norepinephrine and endothelin were comparable in arteries from SHRs and WKY rats of all ages. In summary, endothelium-dependent relaxations of mesenteric arteries from ''prehypertensive'' SHR rats were impaired by the production of a contractile factor (or factors) that appears to be superoxide anions.