Kost C K, Li P, Pfeifer C A, Jackson E K
Center for Clinical Pharmacology, University of Pittsburgh Medical Center, Pennsylvania.
J Pharmacol Exp Ther. 1994 Sep;270(3):1063-70.
In the present study we used radiotelemetry technology to investigate: 1) the time course for development of hypertension in 2-kidney, 1-clip (2K1C) rats and 2) the effect of chronic caffeine consumption on blood pressure in 2K1C rats. Rats received water or caffeine (0.1%) in drinking water and were instrumented with radiotelemetry devices to permit continuous monitoring of blood pressure. A clip was placed on the left renal artery of rats in both the water (WATER/CLIP) and caffeine (CAFFEINE/CLIP) groups. The clip was applied briefly to, then removed from, the renal artery of caffeine- and water-treated rats randomized to the sham-operated (SHAM) group. Mean arterial blood pressure (MABP) increased by approximately 35 mm Hg within 2 hr of clipping. MABP in the WATER/CLIP and CAFFEINE/CLIP groups differed significantly from the SHAM group, but not from each other, for the first 10 days after clipping. Thereafter, MABP was greater in the CAFFEINE/CLIP rats as compared to WATER/CLIP rats. At 4.5 weeks after clipping, MABP values differed significantly in the CAFFEINE/CLIP, WATER/CLIP and SHAM rats (140 +/- 4, 122 +/- 4 and 103 +/- 2 mm Hg, respectively). Involvement of the renin-angiotensin system was assessed by treatment with the AT1 receptor antagonist, losartan, and the converting enzyme inhibitor, captopril. Results from this study indicate: 1) hypertension develops rapidly after clipping in rats monitored with telemetry; 2) the renin-angiotensin system is involved in maintaining hypertension in 2K1C rats even beyond 4 weeks after clipping; and 3) caffeine augments the increase of blood pressure in 2K1C rats, apparently through the involvement of the renin-angiotensin system.
在本研究中,我们使用无线电遥测技术来研究:1)二肾一夹(2K1C)大鼠高血压发展的时间进程,以及2)长期摄入咖啡因对2K1C大鼠血压的影响。大鼠饮用含或不含咖啡因(0.1%)的水,并植入无线电遥测装置以持续监测血压。水(WATER/CLIP)组和咖啡因(CAFFEINE/CLIP)组的大鼠左肾动脉均被夹闭。对随机分配到假手术(SHAM)组的经咖啡因和水处理的大鼠,肾动脉先短暂夹闭,然后再松开。夹闭后2小时内,平均动脉血压(MABP)升高约35 mmHg。夹闭后的前10天,WATER/CLIP组和CAFFEINE/CLIP组的MABP与SHAM组有显著差异,但两组之间无显著差异。此后,与WATER/CLIP组大鼠相比,CAFFEINE/CLIP组大鼠的MABP更高。夹闭后4.5周,CAFFEINE/CLIP组、WATER/CLIP组和SHAM组大鼠的MABP值有显著差异(分别为140±4、122±4和103±2 mmHg)。通过使用AT1受体拮抗剂氯沙坦和转化酶抑制剂卡托普利进行治疗,评估肾素-血管紧张素系统的参与情况。本研究结果表明:1)在用遥测技术监测的大鼠中,夹闭后高血压迅速发展;2)肾素-血管紧张素系统参与维持2K1C大鼠的高血压,即使在夹闭后4周以上;3)咖啡因显然通过肾素-血管紧张素系统的参与,增强了2K1C大鼠血压的升高。