Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure

Kimberly R. Pechman, David P. Basile, Hayley Lund, David L. Mattson

Research output: Contribution to journalArticle

Abstract

The present study determined the effect of immune suppression with mycophenolate mofetil (MMF) on sodium-sensitive hypertension following recovery from ischemia reperfusion (I/R)-induced acute renal failure. Male Sprague-Dawley rats fed 0.4% NaCl chow were subjected to 40 min bilateral I/R or control sham surgery. After 35 days of recovery, when plasma creatinine levels had returned to normal, the rats were switched to 4.0% NaCl chow for 28 days and administered vehicle or MMF (20 mg·kg-1·day-1 ip). High-salt mean arterial pressure was significantly higher in I/R rats (144 ± 16 mmHg) compared with vehicle-treated sham rats (122 ± 2 mmHg). Treatment of I/R rats with MMF during the period of high salt intake prevented the salt-induced increase in arterial pressure (114 ± 3 mmHg). Conscious creatinine clearance was lower in I/R rats (0.27 ± 0.07 ml·min-1·100 g body wt-1) compared with vehicle-treated sham rats (0.58 ± 0.04 ml·min -1·100 g body wt-1); MMF treatment prevented the decrease in creatinine clearance in I/R rats (0.64 ± 0.07 ml·min-1·100 g body wt-1). I/R injury also significantly increased glomerular tissue damage and increased the presence of ED-1 positive (macrophages) and S100A4 positive cells (fibroblasts) in the renal interstitium. The I/R rats treated with MMF exhibited a significant reduction in infiltrating macrophages and fibroblasts and decreased histological damage. The present data indicate that infiltrating immune cells mediate or participate in the development of sodium-sensitive hypertension and renal damage in rats apparently recovered from renal I/R injury.

Original languageEnglish (US)
Pages (from-to)R1234-R1239
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume294
Issue number4
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

Fingerprint

Acute Kidney Injury
Mycophenolic Acid
Sodium
Reperfusion
Hypertension
Ischemia
Creatinine
Salts
Reperfusion Injury
Arterial Pressure
Fibroblasts
Macrophages
Kidney
Renal Hypertension
Sprague Dawley Rats

Keywords

  • Hypertension
  • Ischemia
  • Rats
  • Sodium dependent

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure. / Pechman, Kimberly R.; Basile, David P.; Lund, Hayley; Mattson, David L.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 294, No. 4, 01.04.2008, p. R1234-R1239.

Research output: Contribution to journalArticle

@article{6650e6256a2147b8a52f0b24d85ffc5e,
title = "Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure",
abstract = "The present study determined the effect of immune suppression with mycophenolate mofetil (MMF) on sodium-sensitive hypertension following recovery from ischemia reperfusion (I/R)-induced acute renal failure. Male Sprague-Dawley rats fed 0.4{\%} NaCl chow were subjected to 40 min bilateral I/R or control sham surgery. After 35 days of recovery, when plasma creatinine levels had returned to normal, the rats were switched to 4.0{\%} NaCl chow for 28 days and administered vehicle or MMF (20 mg·kg-1·day-1 ip). High-salt mean arterial pressure was significantly higher in I/R rats (144 ± 16 mmHg) compared with vehicle-treated sham rats (122 ± 2 mmHg). Treatment of I/R rats with MMF during the period of high salt intake prevented the salt-induced increase in arterial pressure (114 ± 3 mmHg). Conscious creatinine clearance was lower in I/R rats (0.27 ± 0.07 ml·min-1·100 g body wt-1) compared with vehicle-treated sham rats (0.58 ± 0.04 ml·min -1·100 g body wt-1); MMF treatment prevented the decrease in creatinine clearance in I/R rats (0.64 ± 0.07 ml·min-1·100 g body wt-1). I/R injury also significantly increased glomerular tissue damage and increased the presence of ED-1 positive (macrophages) and S100A4 positive cells (fibroblasts) in the renal interstitium. The I/R rats treated with MMF exhibited a significant reduction in infiltrating macrophages and fibroblasts and decreased histological damage. The present data indicate that infiltrating immune cells mediate or participate in the development of sodium-sensitive hypertension and renal damage in rats apparently recovered from renal I/R injury.",
keywords = "Hypertension, Ischemia, Rats, Sodium dependent",
author = "Pechman, {Kimberly R.} and Basile, {David P.} and Hayley Lund and Mattson, {David L.}",
year = "2008",
month = "4",
day = "1",
doi = "10.1152/ajpregu.00821.2007",
language = "English (US)",
volume = "294",
pages = "R1234--R1239",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure

AU - Pechman, Kimberly R.

AU - Basile, David P.

AU - Lund, Hayley

AU - Mattson, David L.

PY - 2008/4/1

Y1 - 2008/4/1

N2 - The present study determined the effect of immune suppression with mycophenolate mofetil (MMF) on sodium-sensitive hypertension following recovery from ischemia reperfusion (I/R)-induced acute renal failure. Male Sprague-Dawley rats fed 0.4% NaCl chow were subjected to 40 min bilateral I/R or control sham surgery. After 35 days of recovery, when plasma creatinine levels had returned to normal, the rats were switched to 4.0% NaCl chow for 28 days and administered vehicle or MMF (20 mg·kg-1·day-1 ip). High-salt mean arterial pressure was significantly higher in I/R rats (144 ± 16 mmHg) compared with vehicle-treated sham rats (122 ± 2 mmHg). Treatment of I/R rats with MMF during the period of high salt intake prevented the salt-induced increase in arterial pressure (114 ± 3 mmHg). Conscious creatinine clearance was lower in I/R rats (0.27 ± 0.07 ml·min-1·100 g body wt-1) compared with vehicle-treated sham rats (0.58 ± 0.04 ml·min -1·100 g body wt-1); MMF treatment prevented the decrease in creatinine clearance in I/R rats (0.64 ± 0.07 ml·min-1·100 g body wt-1). I/R injury also significantly increased glomerular tissue damage and increased the presence of ED-1 positive (macrophages) and S100A4 positive cells (fibroblasts) in the renal interstitium. The I/R rats treated with MMF exhibited a significant reduction in infiltrating macrophages and fibroblasts and decreased histological damage. The present data indicate that infiltrating immune cells mediate or participate in the development of sodium-sensitive hypertension and renal damage in rats apparently recovered from renal I/R injury.

AB - The present study determined the effect of immune suppression with mycophenolate mofetil (MMF) on sodium-sensitive hypertension following recovery from ischemia reperfusion (I/R)-induced acute renal failure. Male Sprague-Dawley rats fed 0.4% NaCl chow were subjected to 40 min bilateral I/R or control sham surgery. After 35 days of recovery, when plasma creatinine levels had returned to normal, the rats were switched to 4.0% NaCl chow for 28 days and administered vehicle or MMF (20 mg·kg-1·day-1 ip). High-salt mean arterial pressure was significantly higher in I/R rats (144 ± 16 mmHg) compared with vehicle-treated sham rats (122 ± 2 mmHg). Treatment of I/R rats with MMF during the period of high salt intake prevented the salt-induced increase in arterial pressure (114 ± 3 mmHg). Conscious creatinine clearance was lower in I/R rats (0.27 ± 0.07 ml·min-1·100 g body wt-1) compared with vehicle-treated sham rats (0.58 ± 0.04 ml·min -1·100 g body wt-1); MMF treatment prevented the decrease in creatinine clearance in I/R rats (0.64 ± 0.07 ml·min-1·100 g body wt-1). I/R injury also significantly increased glomerular tissue damage and increased the presence of ED-1 positive (macrophages) and S100A4 positive cells (fibroblasts) in the renal interstitium. The I/R rats treated with MMF exhibited a significant reduction in infiltrating macrophages and fibroblasts and decreased histological damage. The present data indicate that infiltrating immune cells mediate or participate in the development of sodium-sensitive hypertension and renal damage in rats apparently recovered from renal I/R injury.

KW - Hypertension

KW - Ischemia

KW - Rats

KW - Sodium dependent

UR - http://www.scopus.com/inward/record.url?scp=41749105784&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41749105784&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00821.2007

DO - 10.1152/ajpregu.00821.2007

M3 - Article

C2 - 18256138

AN - SCOPUS:41749105784

VL - 294

SP - R1234-R1239

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 4

ER -