Tresham J J, Whitworth J A, Scoggins B A, Bennett W M
Howard Florey Institute of Experimental Physiology and Medicine, Parkville, Victoria, Australia.
Transplantation. 1990 Jan;49(1):144-8. doi: 10.1097/00007890-199001000-00032.
Thromboxanes have been implicated in the CsA-induced hemodynamic changes and impairment in renal function in humans and in rats. We have previously shown that administration of intravenous CsA to sheep for 5 days at 12 mg/kg/day produces a hypertension that is resistance mediated and independent of nephrotoxicity. In this study we used a thromboxane synthetase inhibitor, U63,557A, to examine the role of thromboxanes in the CsA-induced hypertension in the sheep. The thromboxane synthetase inhibitor had no effect on blood pressure in normotensive sheep. Serum thromboxane levels were not elevated with CsA, and the inhibitor had a minimal effect on blood pressure during CsA treatment, suggesting that thromboxanes are not a major contributor to the rise in blood pressure seen in the sheep. A study of the dose-response relationship for CsA at 3, 6, and 24 mg/kg/day for 5 days indicated that maximal blood pressure responses were attained with 6 mg/kg/day.
血栓素与环孢素A（CsA）诱导的人体和大鼠血流动力学变化及肾功能损害有关。我们之前已经表明，以12毫克/千克/天的剂量给绵羊静脉注射CsA 5天会产生一种由阻力介导且与肾毒性无关的高血压。在本研究中，我们使用一种血栓素合成酶抑制剂U63,557A来研究血栓素在CsA诱导的绵羊高血压中的作用。该血栓素合成酶抑制剂对血压正常的绵羊的血压没有影响。环孢素A不会使血清血栓素水平升高，并且该抑制剂在环孢素A治疗期间对血压的影响极小，这表明血栓素并非绵羊血压升高的主要因素。一项对环孢素A以3、6和24毫克/千克/天的剂量持续5天的剂量反应关系研究表明，6毫克/千克/天可达到最大血压反应。
