REGULATION OF ENDOTHELIN EXCRETION

内皮素排泄的调节

• 批准号: 3843358
• 负责人: Z ABASSI
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3843358
• 关键词: angiotensin II; arginine vasopressin; blood pressure; captopril; diuresis; dosage; endothelin; hormone inhibitor; hormone regulation /control mechanism; kidney pharmacology; laboratory rat; nifedipine; saralasin; urination

Endothelin (ET), a potent endogenous vasoconstrictor, is produced by the endothelin. High amounts of ET are found in the urine compared to low levels in plasma. Although much has been learned about the structure and biological effects of ET, little is known about the regulation of the urinary excretion of ET (UETV). We investigated 1) The effects of angiotensin II (A-II), arginine vasopressin (AVP) and nifedipine on UETV. 2) The effects of the non specific A-II antagonist - Saralasin and the specific A-II non peptide antagonist - losartan on the stimulatory effect of A-II on UETV. 3) The effect of converting enzyme inhibition by captopril on the stimulatory effect of nifedipine on the UETV. A-II (50 and 500 ng/kg/min) caused significant increases in urine flow (V), mean arterial pressure (MAP) and 10-30 fold increases in UETV. Pretreatment of the rats with saralasin (1-3 mg) significantly reduced V and MAP but not UETV. Infusion of saralasin alone caused a significant increase in UETV without affecting the MAP or V. Pretreatment of the rats with losartan (10 mg/kg) totally blocked the increases in MAP and UETV induced by A-II. AVP (10 and 100 increases/kg/h) administration induced similar hypertensive and diuretic responses as A-II, but did not alter UETV. Infusion of nifedipine (0.1 and 1.0 mg/kg/h) increased UETV 3-10 fold. Pretreatment of the rats with converting enzyme inhibitor (captopril- 1mg/kg/h) abolished that increase.

内皮素（ET）是一种强有力的内源性血管收缩剂， 内皮素 与低水平相比，在尿液中发现大量的ET 血浆水平。 尽管我们对这种结构已经了解了很多 以及ET的生物学效应，关于ET的调节知之甚少。 尿ET排泄量（UETV）。 我们研究了1）血管紧张素II（A-II）、精氨酸（Arg） 加压素（AVP）和硝苯地平对UETV的影响。 2)非政府组织的影响 特异性A-II拮抗剂- Saralasin和特异性A-II非肽 拮抗剂氯沙坦对A-II对UETV的刺激作用的影响。 3)的 巯甲丙脯酸抑制转化酶对刺激性心肌细胞凋亡的影响 硝苯地平对UETV的影响。 A-II（50和500 ng/kg/min）导致尿流量显著增加 (V)平均动脉压（MAP）和UETV增加10-30倍。 用saralasin（1-3 mg）预处理大鼠显著降低V MAP，而不是UETV。 单独输注saralasin引起了显著的 增加UETV而不影响MAP或V。 预处理 氯沙坦（10 mg/kg）完全阻断MAP的升高， A-II诱导的UETV。 AVP（10和100增加/kg/h）给药 诱导类似的高血压和利尿反应的A-II，但没有 更改UETV。 输注硝苯地平（0.1和1.0 mg/kg/h）使UETV增加3-10倍。 用转换酶抑制剂（captopril- 1 mg/kg/h）消除了这种增加。