Schweda Frank, Wagner Charlotte, Krämer Bernhard K, Schnermann Jürgen, Kurtz Armin
Institut für Physiologie and Klinik und Poliklinik für Innere Medizin, Universität Regensburg, 93040 Regensburg, Germany.
Am J Physiol Renal Physiol. 2003 Apr;284(4):F770-7. doi: 10.1152/ajprenal.00280.2002. Epub 2002 Dec 10.
Recent studies demonstrated that the influence of the macula densa on glomerular filtration is abolished in adenosine A(1) receptor (A(1)AR) knockout mice. Inasmuch as the macula densa not only regulates glomerular filtration but also controls the activity of the renin system, the present study aimed to determine the role of the A(1)AR in macula densa control of renin synthesis and secretion. Although a high-salt diet over 1 wk suppressed renin mRNA expression and renal renin content to similar degrees in A(1)AR(+/+), A(1)AR(+/-), and A(1)AR(-/-) mice, stimulation of Ren-1 mRNA expression and renal renin content by salt restriction was markedly enhanced in A(1)AR(-/-) compared with wild-type mice. Pharmacological blockade of macula densa salt transport with loop diuretics stimulated renin expression in vivo (treatment with furosemide at 1.2 mg/day for 6 days) and renin secretion in isolated perfused mouse kidneys (treatment with 100 microM bumetanide) in all three genotypes to the same extent. Taken together, our data are consistent with the concept of a tonic inhibitory role of the A(1)AR in the renin system, whereas they indicate that the A(1)AR is not indispensable in macula densa control of the renin system.
最近的研究表明，在腺苷A(1)受体（A(1)AR）基因敲除小鼠中，致密斑对肾小球滤过的影响消失。由于致密斑不仅调节肾小球滤过，还控制肾素系统的活性，本研究旨在确定A(1)AR在致密斑对肾素合成和分泌的控制中的作用。尽管为期1周以上的高盐饮食在A(1)AR(+/+)、A(1)AR(+/-)和A(1)AR(-/-)小鼠中对肾素mRNA表达和肾脏肾素含量的抑制程度相似，但与野生型小鼠相比，A(1)AR(-/-)小鼠中盐限制对Ren-1 mRNA表达和肾脏肾素含量的刺激作用明显增强。在所有三种基因型中，用袢利尿剂对致密斑盐转运进行药理学阻断在体内（以1.2 mg/天的剂量给予呋塞米治疗6天）和在离体灌注的小鼠肾脏中（用100 microM布美他尼治疗）对肾素分泌的刺激作用程度相同。综上所述，我们的数据与A(1)AR在肾素系统中具有紧张性抑制作用的概念一致，而它们表明A(1)AR在致密斑对肾素系统的控制中并非不可或缺。
