Uderman H D, Jackson E K, Puett D, Workman R J
J Cardiovasc Pharmacol. 1984 Sep-Oct;6(5):969-72. doi: 10.1097/00005344-198409000-00035.
Treatment of young spontaneously hypertensive rats (SHR) with a thromboxane synthetase inhibitor (TSI) attenuates their subsequent development of hypertension. In this study, treatment of adult SHR during the established phase of hypertension with the TSI UK38,485 (100 mg/kg daily) lowered systolic blood pressure from baseline after 4 days of treatment to a maximum depression of 25 mm Hg on day 10 of the study. Additional confirmation of the fact that this TSI does not lower blood pressure acutely was made via continuous intraarterial recordings in SHR administered their first dose of UK38,485. Urinary dinor-6-keto-PGF1 alpha excretion was measured by a highly specific chemical-ionization, negative-ion GC/MS assay in the selective ion monitoring mode. This metabolite of PGI2 was not significantly affected by 6 days of daily administration of UK38,485 to adult SHR and implies that there was not sufficient endoperoxide shunting to affect total body PGI2 production. The finding that UK38,485 exhibited antihypertensive activity during established SHR hypertension was unexpected and has considerable practical and theoretical significance.
用血栓素合成酶抑制剂（TSI）治疗年轻的自发性高血压大鼠（SHR）可减弱其随后的高血压发展。在本研究中，在高血压确立阶段用TSI UK38,485（每日100 mg/kg）治疗成年SHR，治疗4天后收缩压从基线水平降低，在研究的第10天最大降低25 mmHg。通过对首次给予UK38,485的SHR进行连续动脉内记录，进一步证实了这种TSI不会急性降低血压这一事实。通过高特异性化学电离、负离子GC/MS测定法在选择性离子监测模式下测量尿中双降-6-酮-PGF1α排泄量。对成年SHR每日给予UK38,485 6天，PGI2的这种代谢产物未受到显著影响，这意味着没有足够的内过氧化物分流来影响全身PGI2的产生。UK38,485在已确立的SHR高血压期间表现出抗高血压活性这一发现出乎意料，具有相当大的实践和理论意义。
