Boussairi E H, Sacquet J, Sassard J, Benzoni D
Department of Physiology and Clinical Pharmacology, Centre National de la Recherche Scientifique, Faculty of Pharmacy, Lyon, France.
Am J Physiol. 1994 Nov;267(5 Pt 2):R1190-7. doi: 10.1152/ajpregu.1994.267.5.R1190.
To evaluate the contribution of thromboxane (Tx) A2-prostaglandin (PG) H2 in two-kidney, one-clip Goldblatt hypertension (GH), 26 GH rats were chronically treated (GHT) with a specific TxA2-PGH2 receptor antagonist, CGS-22652 (30 mg.kg-1.24 h-1 sc); 28 others as well as 17 sham-clipped (SC) rats received vehicle. Twelve GH and 3 GHT rats developed malignant hypertension and died. After 6 wk of treatment, GH rats exhibited higher mean blood pressure (BP; 189 +/- 3 vs. 118 +/- 2 mmHg) and an increased vascular reactivity to the main pressor agents compared with SC rats. Chronic TxA2-PGH2 receptor blockade lowered mean BP in 13 GHT rats (125 +/- 3 mmHg) and decreased their vascular reactivity compared with GH rats. However, 10 GHT rats remained hypertensive (190 +/- 9 mmHg) and differed from the former by an increased vascular reactivity to vasopressin. It is concluded that renal artery clipping induces either benign or malignant hypertension. In benign forms, TxA2-PGH2 blockade normalizes BP through decreasing the vascular responsiveness to the main pressor agents. In malignant forms, it limits the elevation of BP and markedly reduces mortality.
为评估血栓素（Tx）A2 - 前列腺素（PG）H2在二肾一夹型Goldblatt高血压（GH）中的作用，26只GH大鼠长期接受特异性TxA2 - PGH2受体拮抗剂CGS - 22652（30 mg·kg-1·24 h-1，皮下注射）治疗（GHT组）；另外28只GH大鼠以及17只假手术夹闭（SC）大鼠接受赋形剂。12只GH大鼠和3只GHT大鼠发展为恶性高血压并死亡。治疗6周后，与SC大鼠相比，GH大鼠表现出更高的平均血压（BP；189±3 vs. 118±2 mmHg）以及对主要升压剂的血管反应性增加。与GH大鼠相比，慢性TxA2 - PGH2受体阻断降低了13只GHT大鼠的平均血压（125±3 mmHg）并降低了它们的血管反应性。然而，10只GHT大鼠仍处于高血压状态（190±9 mmHg），并且与前者不同，它们对血管加压素的血管反应性增加。结论是肾动脉夹闭可导致良性或恶性高血压。在良性高血压中，TxA2 - PGH2阻断通过降低血管对主要升压剂的反应性使血压正常化。在恶性高血压中，它限制血压升高并显著降低死亡率。
