Zou A P, Nithipatikom K, Li P L, Cowley A W
Departments of Physiology and Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Am J Physiol. 1999 Mar;276(3):R790-8. doi: 10.1152/ajpregu.1999.276.3.R790.
This study determined the levels of adenosine in the renal medullary interstitium using microdialysis and fluorescence HPLC techniques and examined the role of endogenous adenosine in the control of medullary blood flow and sodium excretion by infusing the specific adenosine receptor antagonists or agonists into the renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary blood flows were measured using laser-Doppler flowmetry. Analysis of microdialyzed samples showed that the adenosine concentration in the renal medullary interstitial dialysate averaged 212 +/- 5.2 nM, which was significantly higher than 55.6 +/- 5.3 nM in the renal cortex (n = 9). Renal medullary interstitial infusion of a selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 300 pmol. kg-1. min-1, n = 8), did not alter renal blood flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast, renal medullary infusion of the selective A2 receptor blocker 3, 7-dimethyl-1-propargylxanthine (DMPX; 150 pmol. kg-1. min-1, n = 9) decreased outer medullary blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium excretion by 35%. Renal medullary interstitial infusion of adenosine produced a dose-dependent increase in OMBF, IMBF, urine flow, and sodium excretion at doses from 3 to 300 pmol. kg-1. min-1 (n = 7). These effects of adenosine were markedly attenuated by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a selective A3 receptor agonist, N6-benzyl-5'-(N-ethylcarbonxamido)adenosine (300 pmol. kg-1. min-1, n = 6) into the renal medulla had no effect on medullary blood flows or renal function. Glomerular filtration rate and arterial pressure were not changed by medullary infusion of any drugs. Our results indicate that endogenous medullary adenosine at physiological concentrations serves to dilate medullary vessels via A2 receptors, resulting in a natriuretic response that overrides the tubular A1 receptor-mediated antinatriuretic effects.
本研究采用微透析和荧光高效液相色谱技术测定了肾髓质间质中腺苷的水平，并通过向麻醉的Sprague-Dawley大鼠肾髓质中注入特定的腺苷受体拮抗剂或激动剂，研究了内源性腺苷在控制髓质血流和钠排泄中的作用。使用激光多普勒血流仪测量肾皮质和髓质血流。对微透析样本的分析表明，肾髓质间质透析液中的腺苷浓度平均为212±5.2 nM，显著高于肾皮质中的55.6±5.3 nM（n = 9）。肾髓质间质注入选择性A1拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX；300 pmol·kg-1·min-1，n = 8），未改变肾血流，但尿流量增加37%，钠排泄增加42%。相反，肾髓质注入选择性A2受体阻滞剂3,7-二甲基-1-丙炔基黄嘌呤（DMPX；150 pmol·kg-1·min-1，n = 9）使外髓质血流（OMBF）降低28%，内髓质血流（IMBF）降低21%，钠排泄降低35%。肾髓质间质注入腺苷，在3至300 pmol·kg-1·min-1的剂量范围内，可使OMBF、IMBF、尿流量和钠排泄呈剂量依赖性增加（n = 7）。腺苷的这些作用被DMPX预处理显著减弱，但未被DPCPX改变。向肾髓质注入选择性A3受体激动剂N6-苄基-5'-（N-乙基碳酰氨基）腺苷（300 pmol·kg-1·min-1，n = 6）对髓质血流或肾功能无影响。髓质注入任何药物均未改变肾小球滤过率和动脉血压。我们的结果表明，生理浓度的内源性髓质腺苷通过A2受体使髓质血管舒张，导致利钠反应，该反应超过了肾小管A1受体介导的抗利钠作用。
