Kobori Hiroyuki, Nishiyama Akira, Abe Youichi, Navar L Gabriel
Department of Physiology, Tulane University Health Sciences Center, 1430 Tulane Ave, SL39, New Orleans, La 70112-2699, USA.
Hypertension. 2003 Mar;41(3):592-7. doi: 10.1161/01.HYP.0000056768.03657.B4. Epub 2003 Feb 10.
This study was performed to examine whether there is an inappropriate regulation of intrarenal angiotensinogen in Dahl-salt sensitive rats (DS) fed a high salt diet (HS). Dahl salt-resistant rats (DR) and DS were maintained on HS (8% NaCl) or low salt diet (LS, 0.3% NaCl) for 4 weeks. Systolic blood pressure (SBP), measured by tail-cuff plethysmography, was unaltered in DR (DR+HS, 127+/-3 mm Hg, n=5; DR+LS, 126+/-3, n=5); however, SBP was significantly increased in DS+HS (208+/-7, n=9) compared with DS+LS (134+/-2, n=5). HS suppressed plasma renin activity in both strains (0.7+/-0.2 ng of angiotensin I/mL per hour in DS+HS, 3.1+/-0.5 in DS+LS, 0.8+/-0.2 in DR+HS, 5.1+/-0.7 in DR+LS). Plasma angiotensinogen levels, measured by Western blot analysis, were also suppressed by HS in both strains (36 919+/-2170 integrated densitometric unit in DS+HS, 53 028+/-2752 in DS+LS, 44 722+/-1721 in DR+HS, 55782+/-3785 in DR+LS). However, kidney angiotensinogen levels were significantly increased in DS+HS (75 850+/-4171, integrated densitometric unit) compared with DS+LS (47 232+/-3470), DR+HS (44 748+/-8236), and DR+LS (42 504+/-4052). Urinary excretion of angiotensinogen, measured by radioimmunoassay of angiotensin I after incubation with excess renin, had a similar profile. Urinary excretion of angiotensinogen was significantly increased in DS+HS (2958+/-531 pmol/d) compared with DS+LS (56+/-4), DR+HS (31+/-12), and DR+LS (21+/-7). These data indicate that intrarenal angiotensinogen is enhanced in DS+HS, which is reflected by the increased urinary excretion of angiotensinogen. The results suggest that DS on HS have an inappropriate augmentation of intrarenal angiotensinogen, which may contribute to impaired sodium excretion during a high salt diet and the development of hypertension in this strain.
本研究旨在探讨在高盐饮食(HS)喂养的 Dahl 盐敏感大鼠(DS)中,肾内血管紧张素原是否存在调节异常。将 Dahl 盐抵抗大鼠(DR)和 DS 分别给予 HS(8%氯化钠)或低盐饮食(LS,0.3%氯化钠)4 周。通过尾袖体积描记法测量的收缩压(SBP),在 DR 中未发生改变(DR+HS,127±3 mmHg,n = 5;DR+LS,126±3,n = 5);然而,与 DS+LS(134±2,n = 5)相比,DS+HS 中的 SBP 显著升高(208±7,n = 9)。HS 抑制了两种品系的血浆肾素活性(DS+HS 中为 0.7±0.2 ng 血管紧张素 I/毫升·小时,DS+LS 中为 3.1±0.5,DR+HS 中为 0.8±0.2,DR+LS 中为 5.1±0.7)。通过 Western 印迹分析测量的血浆血管紧张素原水平,在两种品系中也受到 HS 的抑制(DS+HS 中为 36 919±2170 积分光密度单位,DS+LS 中为 53 028±2752,DR+HS 中为 44 722±1721,DR+LS 中为 55782±3785)。然而,与 DS+LS(47 232±3470)、DR+HS(44 748±8236)和 DR+LS(42 504±4052)相比,DS+HS 中的肾血管紧张素原水平显著升高(75 850±4171 积分光密度单位)。通过与过量肾素孵育后对血管紧张素 I 进行放射免疫测定来测量的血管紧张素原尿排泄情况,具有相似的特征。与 DS+LS(56±4)、DR+HS(31±12)和 DR+LS(21±7)相比,DS+HS 中的血管紧张素原尿排泄显著增加(2958±531 pmol/d)。这些数据表明,DS+HS 中肾内血管紧张素原增强,这通过血管紧张素原尿排泄增加得以体现。结果提示,HS 喂养的 DS 存在肾内血管紧张素原的不适当增加,这可能导致高盐饮食期间钠排泄受损以及该品系高血压的发生。