Geoffroy J, Benzoni D, Sassard J
Department of Physiology and Clinical Pharmacology, UA CNRS 606, Faculty of Pharmacy, Lyon, France.
J Hypertens Suppl. 1989 Dec;7(6):S272-3. doi: 10.1097/00004872-198900076-00132.
In order to determine whether the increased renal biosynthesis of thromboxane A2, observed in young genetically hypertensive (LH) rats of the Lyon strain, could be involved in the development of their hypertension, 12 LH female rats were given a specific thromboxane A2 receptor antagonist, AH 23848 (Glaxo Group Research) orally (2 mg/kg twice a day) from 3 to 9 weeks of age. In addition, 12 LH and 12 normotensive (LN) rats were given vehicle only (sodium bicarbonate 8%). The thromboxane receptor antagonist AH 23848, which inhibited platelet aggregation by about 65%, did not modify the renal production of thromboxane A2, prostaglandin I2 (PGI2) or prostaglandin E2 (PGE2). It induced a progressive, potent and long lasting decrease in systolic blood pressure which was normalized in 6-, 7- and 8-week-old LH rats, thus demonstrating the involvement of thromboxane A2 in the onset of hypertension in this model. In contrast with thromboxane synthetase inhibitors, the AH 23848 antihypertensive effect persisted 1 week after the cessation of treatment, showing the superiority of thromboxane A2 receptor blockade over thromboxane synthetase inhibition.
为了确定在Lyon品系的年轻遗传性高血压（LH）大鼠中观察到的血栓素A2肾生物合成增加是否与它们高血压的发展有关，12只LH雌性大鼠从3至9周龄开始口服一种特异性血栓素A2受体拮抗剂AH 23848（葛兰素集团研究公司）（2毫克/千克，每天两次）。此外，12只LH大鼠和12只血压正常（LN）大鼠仅给予赋形剂（8%碳酸氢钠）。血栓素受体拮抗剂AH 23848可抑制血小板聚集约65%，但并未改变血栓素A2、前列腺素I2（PGI2）或前列腺素E2（PGE2）的肾脏生成。它引起收缩压进行性、强效且持久的下降，6周、7周和8周龄的LH大鼠收缩压恢复正常，从而证明在该模型中血栓素A2参与了高血压的发病。与血栓素合成酶抑制剂不同，AH 23848的降压作用在停药1周后仍然持续，表明血栓素A2受体阻断优于血栓素合成酶抑制。
