Effects of thromboxane synthase inhibition on vascular responsiveness in the in vivo rat mesentery.
Effects of thromboxane synthase inhibition on vascular responsiveness in the in vivo rat mesentery.
复制标题
血栓素合酶抑制对体内大鼠肠系膜血管反应性的影响。
DOI：
10.1172/jci112238
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Jackson,EK
中科院分区：
文献类型：
--
作者：
Jackson,EK
本研究的目的是确定血栓素合酶抑制对血管反应性的影响。为了实现这一目标，在体内测定血栓素合酶抑制剂对交感神经刺激、去甲肾上腺素和血管紧张素II的肠系膜血管反应的影响。在血压正常的大鼠中，用血栓素合酶抑制剂UK 38，485（100 mg/kg × d × 7 d）长期治疗可减弱血管对神经刺激和血管紧张素II的反应，但对去甲肾上腺素无影响。吲哚美辛治疗（5 mg/kg × 3次给药）不减弱血管反应，但可防止长期给予UK 38，485减弱血管反应性。单次给药UK 38，485（100 mg/kg）不会改变血管对神经刺激或血管紧张素II的反应，即使血小板血栓素合酶被完全抑制。在自发性高血压大鼠中，长期给予（100 mg/kg × d × 7 d）UK 38、485、OKY 1581或U-63557 A（三种结构不同的血栓烷合酶抑制剂）可减弱血管对神经刺激和血管紧张素II的反应。只有U-63557 A抑制对去甲肾上腺素的反应。UK 38，485或U-63557 A的长期治疗不影响吲哚美辛治疗的高血压大鼠的血管反应性。此外，长期给予较低剂量的UK 38、485或U-63557 A（30 mg/kg × d × 7 d），尽管可完全阻断血小板血栓烷合酶，但不影响高血压大鼠的血管反应性。这些数据表明，长期给予高剂量血栓烷合酶抑制剂可减弱血管对交感神经刺激和血管紧张素II的反应，但通常不会减弱对去甲肾上腺素的反应。该作用可通过血管壁内的内过氧化物分流来介导。
The purpose of this investigation was to determine the effects of thromboxane synthase inhibition on vascular responsiveness. To achieve this goal, the effects of thromboxane synthase inhibitors on mesenteric vascular responses to sympathetic nerve stimulation, norepinephrine, and angiotensin II were determined in vivo. In normotensive rats, chronic treatment with the thromboxane synthase inhibitor, UK38,485 (100 mg/kg X d X 7 d), attenuated vascular responses to nerve stimulation and angiotensin II, but not to norepinephrine. Indomethacin treatment (5 mg/kg X three doses) did not attenuate vascular responses, but did prevent chronic UK38,485 administration from attenuating vascular reactivity. A single dose of UK38,485 (100 mg/kg) did not modify vascular responses to nerve stimulation or angiotensin II, even though platelet thromboxane synthase was inhibited completely. In spontaneously hypertensive rats, chronic administration (100 mg/kg X d X 7 d) of either UK38,485, OKY1581, or U-63557A (three structurally distinct thromboxane synthase inhibitors) attenuated vascular responses to nerve stimulation and angiotensin II. Only U-63557A suppressed responses to norepinephrine. Chronic treatment with UK38,485 or U-63557A did not influence vascular reactivity in hypertensive rats treated with indomethacin. Also, chronic administration of lower doses of UK38,485 or U-63557A (30 mg/kg X d X 7 d) did not affect vascular responsiveness in hypertensive rats, despite complete blockade of platelet thromboxane synthase. These data indicate that chronic administration of high doses of thromboxane synthase inhibitors attenuates vascular responses to sympathetic nerve stimulation and angiotensin II, but not usually to norepinephrine. This action may be mediated by endoperoxide shunting within the blood vessel wall.