LEUKOTRIENES, PROSTACYCLIN, BLOOD VESSELS

据报道，自发性高血压大鼠(SHR) 有二十烷类化合物几种酶系统的异常 新陈代谢。这些异常包括：1)血管强化 磷脂酶A2(PLA2)活性；2)增强肾脏细胞色素 P450酶活性：3)尿PGF2α排泄量增加； 4)提高了维管植物PGI2的产量；5)增加了产量 血小板12-脂氧合酶对12-HETE的抑制作用。然而，这些课程 而SHR这些异常的机制仍然存在 未知。在这个提案中，我们将评估关键的酶 负责这些产品的生成和转换 二十烷类化合物。 将进行以下实验： 1.自发性高血压大鼠血管和肾脏磷脂酶A2活性的研究 以及它们与高血压发病的关系。 2.12-HPETE和15-HPETE的转化研究 由“氢过氧化氢裂解酶”产生 C-12和C-14短链醛及其结构研究 生物活动。 3.血管中11-酮还原酶活性的研究 自发性高血压大鼠肾脏与9α、11β-受体的发生 自发性高血压大鼠尿中的PGF2替代了PGF2a。 4.维管束“环氧合酶(PGH-Synthase)”的研究 和“PGI2-合成酶”活性和酶水平 SHR。 5.PGI2转化为5(6)-氧化-PGI2的研究 自发性高血压大鼠细胞色素P450环氧合酶系统。 6.红豆杉的分子生物学和细胞生物学研究 SHR中的“环氧合酶”。 在这项特殊的研究中，肾脏细胞色素的特征 SHR和WKY的P450环氧合酶及其特异性抗体 会产生环氧合酶。转录和/或更改 环氧合酶基因的翻译将通过Northern和 Western斑点杂交技术与一个肾脏的cDNA克隆，这将 在研究过程中做好准备。 对其作用机制、酶水平和细胞周期的认识 自发性高血压患者这些酶系统的遗传调节可能导致 高血压病的防治进展。

It has been reported that spontaneously hypertensive rats (SHR) have abnormalities of several enzyme systems of eicosanoid metabolism. These abnormalities include: 1) enhanced vascular phospholipase A2 (PLA2) activity; 2) enhanced renal cytochrome P450 enzyme activity; 3) increased output of urinary PGF2alpha; 4) enhanced production of vascular PGI2; 5) increased production of 12-HETE by platelet 12-lipoxygenase. However, the courses and mechanisms involved in these abnormalities in SHR remain unknown. In this proposal we will evaluate the key enzymes responsible for the generation and transformation of these eicosanoids. The following experiments will be performed: 1. Studies on the vascular and renal PLA2 activities of SHR and their relationship to the development of hypertension. 2. Studies of the transformation of 12-HPETE and 15-HPETE by the enzyme "Hydroperoxide Lyase" for the generation of C-12 and C-14 short chain aldehydes and studies of their biological activities. 3. Studies of the activity of 11-ketoreductase in blood vessels and kidney of SHR and the occurance of 9alpha, 11beta- PGF2 instead of PGF2alpha in the urine of SHR. 4. Studies of the vascular "cyclo-oxygenase (PGH-synthase)" and "PGI2-synthase" activities and the enzyme levels in SHR. 5. Studies of the conversion of PGI2 to 5(6)-oxido-PGI2 via the cytochrome P450 epoxygenase system in SHR. 6. Studies of the molecular and cellular biology of "epoxygenase" in SHR. In this particular study, characterization of the renal cytochrome P450 epoxygenase from SHR and WKY and specific antibodies to epoxygenase will be made. Changes in transcription and/or translation of epoxygenase genes will be shown by Northern- and Western dot-blot technique with a renal cDNA clone, which will be prepared in the course of this study. The understanding of the mechanism, enzyme levels and the genetic regulation of these enzyme systems in SHR may lead to the development and treatment for prevention of hypertension.