Ohnishi A, Li P, Branch R A, Biaggioni I O, Jackson E K
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Hypertension. 1988 Aug;12(2):152-61. doi: 10.1161/01.hyp.12.2.152.
Our previous studies support the hypothesis that activation of the renin-angiotensin system by renal ischemia elevates adenosine levels and that adenosine acts in a negative feedback loop to limit renin release and to mitigate some of the hypertension-producing effects of angiotensin II. To further test this hypothesis, we compared the time course of caffeine-induced increases in plasma renin activity with the time course of changes in plasma levels of adenosine in two models of renin-dependent renovascular hypertension. Also, we compared the effects of caffeine on plasma renin activity and arterial blood pressure in renin-dependent versus renin-independent renovascular hypertension. In comparison to sham-operated rats, plasma levels of adenosine in the left and right renal veins and aorta were elevated severalfold in two-kidney, one clip rats (2K1C) 1 week after left renal artery clipping. However, adenosine levels declined during the second and third weeks after clipping. In 2K1C rats treated chronically with caffeine, plasma renin activity was markedly elevated during the first week after operation as compared to non-caffeine-treated 2K1C rats. However, during the second and third weeks after clipping, caffeine had lesser effects on plasma renin activity. A temporal relationship between plasma adenosine levels and caffeine-induced hyperreninemia was also observed in rats with aortic ligation. Caffeine accelerated hypertension in 2K1C rats and rats with aortic ligation (renin-dependent renovascular hypertension), but it had no effect on plasma renin activity or blood pressure in one-kidney, one clip rats (renin-independent renovascular hypertension). These results lend further support to the hypothesis that adenosine functions to mitigate the renin-angiotensin system in renin-dependent renovascular hypertension.
我们之前的研究支持这样的假设，即肾缺血激活肾素 - 血管紧张素系统会升高腺苷水平，且腺苷通过负反馈回路作用来限制肾素释放，并减轻血管紧张素II产生高血压的部分效应。为了进一步验证这一假设，我们在两种肾素依赖性肾血管性高血压模型中，比较了咖啡因诱导的血浆肾素活性增加的时间进程与血浆腺苷水平变化的时间进程。此外，我们还比较了咖啡因对肾素依赖性与肾素非依赖性肾血管性高血压中血浆肾素活性和动脉血压的影响。与假手术大鼠相比，在左肾动脉夹闭1周后的二肾一夹大鼠（2K1C）中，左、右肾静脉和主动脉中的血浆腺苷水平升高了数倍。然而，夹闭后第二周和第三周腺苷水平下降。在长期用咖啡因治疗的2K1C大鼠中，与未用咖啡因治疗的2K1C大鼠相比，术后第一周血浆肾素活性明显升高。然而，在夹闭后第二周和第三周，咖啡因对血浆肾素活性的影响较小。在主动脉结扎的大鼠中也观察到血浆腺苷水平与咖啡因诱导的高肾素血症之间的时间关系。咖啡因加速了2K1C大鼠和主动脉结扎大鼠（肾素依赖性肾血管性高血压）的高血压进程，但对一肾一夹大鼠（肾素非依赖性肾血管性高血压）的血浆肾素活性或血压没有影响。这些结果进一步支持了腺苷在肾素依赖性肾血管性高血压中发挥减轻肾素 - 血管紧张素系统作用的假设。
