Lo M, Medeiros I A, Mullins J J, Ganten D, Barres C, Cerutti C, Vincent M, Sassard J
Department of Physiology and Clinical Pharmacology, Unité de Recherche Associée Centre National de la Recherche Scientifique 1483, Faculty of Pharmacy, Lyon, France.
Am J Physiol. 1993 Jul;265(1 Pt 2):R180-6. doi: 10.1152/ajpregu.1993.265.1.R180.
The present work was aimed to assess the factors involved in the maintenance of hypertension in adult transgenic mRen-2 (TG) rats. Special attention was paid to the renal handling of sodium, the sympathetic, and the renin-angiotensin system (RAS) activity. TG rats were compared with age-matched Lyon genetically hypertensive rats (LH), as both are of Sprague-Dawley origin. Blood pressure (BP), heart rate, and renal sympathetic nerve activity (RSNA) were recorded in conscious freely moving animals. Kidneys were isolated and single-pass perfused at different pressure levels. It was observed that the peripheral sympathetic drive was identical in TG and LH rats as indicated by their similar 24-h urinary excretion of catecholamines and methoxylated metabolites, baseline RSNA and its control by the baroreflex, and hypotensive response to ganglion-blockade. On the contrary, TG rats differed from LH rats by a more rapid excretion of an oral isotonic sodium load, a greater hypotensive and natriuretic response to furosemide, and a more marked BP response to acute RAS blockade. The TG kidney responses to stepwise changes in renal perfusion pressure (RPP) differed from those of LH rats by significantly higher perfusate flow and glomerular filtration rate. However, the pressure natriuresis curve of TG kidneys did not differ from that of LH rats because of an elevated tubular sodium reabsorption rate. These results suggest that adult TG rats, compared with LH rats, exhibit a tendency toward sodium and water retention, which may explain that despite low renal and circulating renin levels, the RAS remains involved in the maintenance of high BP in that model.
本研究旨在评估成年转基因mRen-2（TG）大鼠维持高血压的相关因素。特别关注了钠的肾脏处理、交感神经以及肾素-血管紧张素系统（RAS）的活性。将TG大鼠与年龄匹配的里昂遗传性高血压大鼠（LH）进行比较，因为两者均源于Sprague-Dawley大鼠。在清醒自由活动的动物中记录血压（BP）、心率和肾交感神经活性（RSNA）。分离肾脏并在不同压力水平下进行单通道灌注。观察到，TG大鼠和LH大鼠的外周交感神经驱动相同，这体现在它们相似的儿茶酚胺和甲氧基化代谢产物的24小时尿排泄量、基线RSNA及其压力反射控制，以及对神经节阻断的降压反应。相反，TG大鼠与LH大鼠的不同之处在于，口服等渗钠负荷后排泄更快，对呋塞米的降压和利钠反应更大，对急性RAS阻断的BP反应更明显。TG肾脏对肾灌注压（RPP）逐步变化的反应与LH大鼠不同，表现为灌注液流量和肾小球滤过率显著更高。然而，由于肾小管钠重吸收率升高，TG肾脏的压力利尿曲线与LH大鼠并无差异。这些结果表明，与LH大鼠相比，成年TG大鼠表现出钠和水潴留的倾向，这可能解释了尽管肾脏和循环肾素水平较低，但RAS仍参与该模型中高血压的维持。
