Nuglozeh E, Mbikay M, Stewart D J, Legault L
Department of Medicine, Hôpital St.-Luc, Université de Montréal, Quebec, Canada.
Am J Physiol. 1997 Oct;273(4):C1427-34. doi: 10.1152/ajpcell.1997.273.4.C1427.
In our previous studies, we found that the atrial natriuretic peptide (ANP) binding and guanylyl cyclase activity of A-type natriuretic peptide receptors (NPR-A) were upregulated in renal papillae but downregulated in vascular tissues and glomeruli of rats with deoxycorticosterone acetate (DOCA)-salt hypertension [E. Nuglozeh, G. Gauquelin, R. Garcia, J. Tremblay, and E. L. Schiffrin. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28): F130-F137, 1990]. To further understand the molecular significance of these regulations, we measured the relative abundance of the transcripts of NPR-A and NPR-B by Northern blot in the aorta, mesenteric arteries, adrenal cortex, renal papillae, and lungs in DOCA-salt hypertensive and control rats. In renal papillae we also examined the translation and transcription of NPR-A by ribosome loading and run-on assay. Compared with controls, the steady-state levels of mRNA for NPR-A were increased in the aorta and mesenteric arteries but were decreased in the adrenal cortex and renal papillae in DOCA-salt-treated rats. NPR-B mRNA was decreased in the aorta, mesenteric arteries, and adrenal cortex in hypertensive rats. In lungs the mRNA for both receptors was unchanged. Translation of NPR-A mRNA, as assessed by ribosome loading, was reduced in renal papillae. Transcriptional activity of its gene was not detectable in these tissues. Guanosine 3',5'-cyclic monophosphate levels generated by NPR-A in renal papillae and by NPR-A and NPR-B in the adrenal cortex, aorta, and mesenteric arteries of DOCA-salt-treated rats remained increased in hypertension. The higher NPR-A activity in the presence of a lower level of its mRNA in renal papillae and the higher NPR-B activity in the presence of a lower level of its mRNA in the vasculature, adrenal cortex, and lungs can alternatively be explained by receptor stabilization or increased receptor recycling.
在我们之前的研究中，我们发现，在醋酸脱氧皮质酮（DOCA）-盐性高血压大鼠的肾乳头中，A型利钠肽受体（NPR-A）的心房利钠肽（ANP）结合及鸟苷酸环化酶活性上调，但在血管组织和肾小球中则下调[E. Nuglozeh, G. Gauquelin, R. Garcia, J. Tremblay, and E. L. Schiffrin. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28): F130-F137, 1990]。为了进一步了解这些调节的分子意义，我们通过Northern印迹法测定了DOCA-盐性高血压大鼠和对照大鼠的主动脉、肠系膜动脉、肾上腺皮质、肾乳头及肺中NPR-A和NPR-B转录本的相对丰度。在肾乳头中，我们还通过核糖体加载和连续分析检测了NPR-A的翻译和转录情况。与对照相比，DOCA-盐处理大鼠的主动脉和肠系膜动脉中NPR-A的mRNA稳态水平升高，但肾上腺皮质和肾乳头中则降低。高血压大鼠的主动脉、肠系膜动脉及肾上腺皮质中NPR-B的mRNA减少。肺中两种受体的mRNA均未改变。通过核糖体加载评估，肾乳头中NPR-A mRNA的翻译减少。在这些组织中未检测到其基因的转录活性。DOCA-盐处理大鼠的肾乳头中NPR-A以及肾上腺皮质、主动脉和肠系膜动脉中NPR-A和NPR-B产生的3',5'-环磷酸鸟苷水平在高血压状态下仍保持升高。肾乳头中NPR-A活性较高而其mRNA水平较低，血管、肾上腺皮质和肺中NPR-B活性较高而其mRNA水平较低，这可以通过受体稳定或受体再循环增加来解释。
