Yagil Y
Nephrology Unit, University of Rochester School of Medicine, New York.
J Pharmacol Exp Ther. 1994 Feb;268(2):826-35.
The effects of adenosine on glomerular filtration rate and renal blood flow are well documented, but its effects on water and sodium excretion are less well established. Previous studies in the rat have shown that i.v. and intra-aortic administration of adenosine decrease water and sodium excretion. The validity of these findings was challenged recently when it was found that intrarenal administration of adenosine in the rat induced marked diuresis and natriuresis. The aim of the current study was to investigate further the effects of intrarenal administration of adenosine on renal excretory function in the rat. Intrarenal infusion of 2 to 15 micrograms/min of adenosine, although having no effect on systemic arterial pressure, induced a 4-fold increase in water and sodium excretion. Intravenous infusion of adenosine at equivalent doses in the same species and under similar experimental conditions resulted in a 1-fold increase in water excretion, and only a transient increase in sodium excretion, whereas intraaortic adenosine had no effect on either variable. During infusion of adenosine by all three routes, there was a significant decline in glomerular filtration rate, but no change in renal plasma flow. The diuretic and natriuretic effects of adenosine during intrarenal infusion were of a similar order of magnitude in animals maintained for 3 weeks on no sodium, normal sodium or high sodium diet, and did not correlate with plasma renin activity. Simultaneous infusion of 10(-7) M 9-cyclopentyl-1,3-dipropylxanthine, a selective adenosine A1 receptor antagonist, markedly inhibited the diuretic and natriuretic effects of intrarenal adenosine. Intrarenal infusion of N6-cyclohexyladenosine, an adenosine A1 receptor agonist, but not of N' ethylcarboxamidoadenosine, a potent A2 receptor agonist, significantly increased water and sodium excretion. These findings suggest that, in the rat, the diuretic and natriuretic effects of adenosine are 1) fully expressed only during intrarenal administration, 2) absent during intra-aortic administration, 3) not related to prior sodium intake or sodium balance, 4) mediated by the adenosine A1 receptor and 5) dissociated from its effects on glomerular filtration and renal plasma flow.
腺苷对肾小球滤过率和肾血流量的影响已有充分记载，但其对水和钠排泄的影响尚不明确。以往在大鼠身上的研究表明，静脉注射和主动脉内注射腺苷会减少水和钠的排泄。然而，最近当发现给大鼠肾内注射腺苷会引起明显的利尿和利钠作用时，这些研究结果的有效性受到了质疑。本研究的目的是进一步探讨肾内注射腺苷对大鼠肾脏排泄功能的影响。肾内输注2至15微克/分钟的腺苷，尽管对全身动脉压没有影响，但会使水和钠的排泄增加4倍。在相同物种和相似实验条件下，静脉输注等量剂量的腺苷会使水排泄增加1倍，钠排泄仅短暂增加，而主动脉内注射腺苷对这两个变量均无影响。通过所有三种途径输注腺苷期间，肾小球滤过率显著下降，但肾血浆流量没有变化。在无钠、正常钠或高钠饮食下维持3周的动物中，肾内输注腺苷时的利尿和利钠作用幅度相似，且与血浆肾素活性无关。同时输注10(-7)M 9 - 环戊基 - 1,3 - 二丙基黄嘌呤，一种选择性腺苷A1受体拮抗剂，可显著抑制肾内腺苷的利尿和利钠作用。肾内输注N6 - 环己基腺苷，一种腺苷A1受体激动剂，但不是N' - 乙基羧酰胺腺苷，一种强效A2受体激动剂，会显著增加水和钠的排泄。这些发现表明，在大鼠中，腺苷的利尿和利钠作用：1）仅在肾内给药时充分表现；2）主动脉内给药时不存在；3）与先前的钠摄入量或钠平衡无关；4）由腺苷A1受体介导；5）与其对肾小球滤过和肾血浆流量的影响无关。
