Tseng C J, Kuan C J, Chu H, Tung C S
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Life Sci. 1993;52(10):883-90. doi: 10.1016/0024-3205(93)90518-8.
Animals treated acutely with an adenosine receptor antagonist have elevated plasma renin activity. This observation suggests that endogenous adenosine plays a physiologically significant role in restraining renin release. However, it is unclear whether chronic blockade of adenosine receptors would cause a rise of renin activity since tolerance to adenosine blockade is known to develop quickly. An earlier study partially addressed this question by showing that chronic blockade of adenosine receptors with caffeine exacerbated both the rise of plasma renin activity and the decline of renal function in 2-kidney-1-clip (2K1C) renovascular hypertensive rats. However, that study did not determine whether the difference in renin activity occurred solely as a secondary result of the difference in renal function. The purpose of this study was to reexamine the effect of chronic caffeine consumption on plasma renin activity and angiotensin I levels in animals in another high-renin model, i.e., the low sodium diet. The low sodium diet is devoid of the potential confounding effect of deteriorating renal function associated with the 2K1C renovascular hypertension model. In this study, animals received normal rat chow and drank either 0.1% caffeine water or vehicle for ten days. After ten days, all rats were switched to a low sodium diet for three weeks. Plasma renin activity and plasma angiotensin I levels were measured before, and at 1 and 3 weeks after initiating the low sodium diet. The results of this study show that chronic blockade of adenosine receptors with 0.1% caffeine water increases plasma renin activity and angiotensin I concentration before and throughout the three weeks when animals were on the low sodium diet. The results of this study suggest that the inhibitory role of adenosine on renin release is a general physiological process, rather than a special situation applicable only to the 2K1C model.
用腺苷受体拮抗剂进行急性处理的动物，其血浆肾素活性会升高。这一观察结果表明，内源性腺苷在抑制肾素释放方面发挥着生理上的重要作用。然而，由于已知对腺苷阻断的耐受性会迅速产生，所以尚不清楚腺苷受体的慢性阻断是否会导致肾素活性升高。一项较早的研究部分解决了这个问题，该研究表明，用咖啡因对腺苷受体进行慢性阻断会加剧两肾一夹（2K1C）肾血管性高血压大鼠的血浆肾素活性升高和肾功能下降。然而，该研究并未确定肾素活性的差异是否仅仅是肾功能差异的继发结果。本研究的目的是在另一种高肾素模型即低钠饮食的动物中，重新审视长期摄入咖啡因对血浆肾素活性和血管紧张素I水平的影响。低钠饮食不存在与2K1C肾血管性高血压模型相关的肾功能恶化的潜在混杂效应。在本研究中，动物接受正常大鼠饲料，并饮用0.1%的咖啡因水或溶剂，持续10天。10天后，所有大鼠改为低钠饮食3周。在开始低钠饮食前、1周和3周时测量血浆肾素活性和血浆血管紧张素I水平。本研究结果表明，在动物食用低钠饮食的前3周及整个期间，用0.1%的咖啡因水对腺苷受体进行慢性阻断会增加血浆肾素活性和血管紧张素I浓度。本研究结果表明，腺苷对肾素释放的抑制作用是一个普遍的生理过程，而非仅适用于2K1C模型的特殊情况。
