Impaired pressure natriuresis resulting in salt-sensitive hypertension is caused by tubulointerstitial immune cell infiltration in the kidney

被引:64
作者
Franco, Martha [1 ]
Tapia, Edilia [1 ]
Bautista, Rocio [1 ]
Pacheco, Ursino [1 ]
Santamaria, Jose [1 ]
Quiroz, Yasmir [2 ]
Johnson, Richard J. [3 ]
Rodriguez-Iturbe, Bernardo [2 ,4 ]
机构
[1] Inst Nacl Cardiol Ignacio Chavez, Dept Nephrol, Mexico City, DF, Mexico
[2] Inst Venezolano Invest Cient Zulia, Maracaibo, Venezuela
[3] Univ Colorado, Div Renal Dis & Hypertens, Denver, CO 80202 USA
[4] Univ Hosp, Renal Serv, Maracaibo, Venezuela
关键词
angiotensin II-positive cells; lymphocytes; macrophages; mycophenolate mofetil; urinary sodium excretion; MYCOPHENOLATE-MOFETIL PREVENTS; NITRIC-OXIDE SYNTHESIS; RENIN-ANGIOTENSIN SYSTEM; BLOOD-PRESSURE; OXIDATIVE STRESS; INTERSTITIAL INFLAMMATION; RENAL AUTOREGULATION; MECHANISMS; PATHOGENESIS; DISEASE;
D O I
10.1152/ajprenal.00463.2012
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Franco M, Tapia E, Bautista R, Pacheco U, Santamaria J, Quiroz Y, Johnson RJ, Rodriguez-Iturbe B. Impaired pressure natriuresis resulting in salt-sensitive hypertension is caused by tubulointerstitial immune cell infiltration in the kidney. Am J Physiol Renal Physiol 304: F982-F990, 2013. First published January 30, 2013; doi: 10.1152/ajprenal.00463.2012.-Immune cell infiltration of the kidney is a constant feature in salt-sensitive hypertension (SSHTN). We evaluated the relationship between the renal inflammation and pressure natriuresis in the model of SSHTN that results from transient oral administration of N omega-nitro-L-arginine methyl ester (L-NAME). Pressure natriuresis was determined in Wistar rats that received 4 wk of a high-salt (4% NaCl) diet, starting 1 wk after stopping L-NAME, which was administered alone (SSHTN group, n = 17) or in association with mycophenolate mofetil (MMF; MMF group, n = 15). The administration of MMF in association with L-NAME is known to prevent the subsequent development of SSHTN. Control groups received a high (n = 12)- and normal (0.4%)-salt diet (n = 20). Rats with SSHTN had increased expression of inflammatory cytokines and oxidative stress. The severity of hypertension correlated directly (P < 0.0001) with the number of tubulointerstitial immune cells and angiotensin II-expressing cells. Pressure natriuresis was studied at renal arterial pressures (RAPs) of 90, 110, 130, and 150 mmHg. Glomerular filtration rate was similar and stable in all groups, and renal blood flow was decreased in the SSHTN group. Significantly decreased natriuresis (P < 0.05) was found in the SSHTN group at RAPs of 130 and 150 mmHg, and there was an inverse correlation (P < 0.01) between the urinary sodium excretion and the number of tubulointerstitial inflammatory cells (lymphocytes and macrophages) and cells expressing angiotensin II. We conclude that tubulointerstitial inflammation plays a key role in the impairment of pressure natriuresis that results in salt-dependent hypertension in this experimental model.
引用
收藏
页码:F982 / F990
页数:9
相关论文
共 53 条
  • [1] AUTO-REGULATION OF RENAL BLOOD-FLOW IN SPONTANEOUSLY HYPERTENSIVE RATS
    ARENDSHORST, WJ
    [J]. CIRCULATION RESEARCH, 1979, 44 (03) : 344 - 349
  • [2] CHRONIC BLOCKADE OF NITRIC-OXIDE SYNTHESIS IN THE RAT PRODUCES SYSTEMIC HYPERTENSION AND GLOMERULAR DAMAGE
    BAYLIS, C
    MITRUKA, B
    DENG, A
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (01) : 278 - 281
  • [3] Oxidative stress alters renal D1 and AT1 receptor functions and increases blood pressure in old rats
    Chugh, Gaurav
    Lokhandwala, Mustafa F.
    Asghar, Mohammad
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2011, 300 (01) : F133 - F138
  • [4] Lymphocyte responses exacerbate angiotensin II-dependent hypertension
    Crowley, Steven D.
    Song, Young-Soo
    Lin, Eugene E.
    Griffiths, Robert
    Kim, Hyung-Suk
    Ruiz, Phillip
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2010, 298 (04) : R1089 - R1097
  • [5] DAVIDSON WD, 1963, J LAB CLIN MED, V62, P351
  • [6] Renal angiotensin II concentration and interstitial infiltration of immune cells are correlated with blood pressure levels in salt-sensitive hypertension
    Franco, Martha
    Martinez, Flavio
    Quiroz, Yasmir
    Galicia, Othir
    Bautista, Rocio
    Johnson, Richard J.
    Rodriguez-Iturbe, Bernardo
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2007, 293 (01) : R251 - R256
  • [7] Angiotensin II, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension
    Franco, Martha
    Martinez, Flavio
    Rodriguez-Iturbe, Bernardo
    Johnson, Richard J.
    Santamaria, Jose
    Montoya, Angelica
    Nepomuceno, Tomas
    Bautista, Rocio
    Tapia, Edilia
    Herrera-Acosta, Jaime
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2006, 291 (06) : F1281 - F1287
  • [8] Mechanisms of pressure natriuresis
    Granger, JP
    Alexander, BT
    Llinas, M
    [J]. CURRENT HYPERTENSION REPORTS, 2002, 4 (02) : 152 - 159
  • [9] BLOOD-PRESSURE CONTROL - SPECIAL ROLE OF THE KIDNEYS AND BODY-FLUIDS
    GUYTON, AC
    [J]. SCIENCE, 1991, 252 (5014) : 1813 - 1816
  • [10] Inflammation, Immunity, and Hypertension
    Harrison, David G.
    Guzik, Tomasz J.
    Lob, Heinrich E.
    Madhur, Meena S.
    Marvar, Paul J.
    Thabet, Salim R.
    Vinh, Antony
    Weyand, Cornelia M.
    [J]. HYPERTENSION, 2011, 57 (02) : 132 - 140