Interactions between oxidative stress and inflammation in salt-sensitive hypertension

Abstract

Tian N, Moore RS, Braddy S, Rose RA, Gu JW, Hughson MD, Manning RD Jr. Interactions between oxidative stress and inflammation in salt-sensitive hypertension. Am J Physiol Heart Circ Physiol 293: H3388-H3395, 2007. First published October 5, 2007; doi:10.1152/ajpheart.00981.2007.-The goal of this study was to test the hypothesis that increases in oxidative stress in Dahl S rats on a high-salt diet help to stimulate renal nuclear factor-B (NF-B), renal proinflammatory cytokines, and chemokines, thus contributing to hypertension, renal damage, and dysfunction. We specifically studied whether antioxidant treatment of Dahl S rats on high Na intake would decrease renal inflammation and thus attenuate the hypertensive and adverse renal responses. Sixty-four 7-to 8-wk-old Dahl S or R/Rapp strain rats were maintained for 5 wk on high Na (8%) or high Na ϩ vitamins C (1 g/l in drinking water) and E (5,000 IU/kg in food). Arterial and venous catheters were implanted at day 21. By day 35 in the high-Na S rats, antioxidant treatment significantly increased the renal reduced-to-oxidized glutathione ratio and decreased renal cortical H 2O2 and O2•Ϫ release and renal NF-B. Antioxidant treatment with vitamins C and E in high-Na S rats also decreased renal monocytes/macrophages in the glomeruli, cortex, and medulla, decreased tumor necrosis factor-␣ by 39%, and decreased monocyte chemoattractant protein-1 by 38%. Vitamin-treated, high-Na S rats also experienced decreases in arterial pressure, urinary protein excretion, renal tubulointerstitial damage, and glomerular necrosis and increases in glomerular filtration rate and renal plasma flow. In conclusion, antioxidant treatment of high-Na Dahl S rats decreased renal inflammatory cytokines and chemokines, renal immune cells, NF-B, and arterial pressure and improved renal function and damage. renal failure; cytokines; chemokines; renal hemodynamics; salt-sensitivity; nuclear factor-B STUDIES IN HUMAN AND EXPERIMENTAL HYPERTENSION have shown that increases in oxidative stress may play an important role in the etiology and maintenance of increased blood pressure. Increased oxidative stress has been found in the spontaneously hypertensive rat (SHR), the stroke-prone SHR, DOCA-salt hypertensive rats, and the Dahl salt-sensitive (S) rat (5,6,10,21,22,41,49). In addition, evidence for increased renal oxidative stress has been found in lead-induced hypertension (48), coarctation of the aorta (3), and in the Dahl S rat (22, 43).There is considerable evidence for the involvement of the immune system in hypertension. Studies in several models of experimental hypertension have found renal invasion of lymphocytes and macrophages (24,29,31,40,45). Anti-immune therapy administered to these models of hypertension successfully decreased arterial pressure (32) and renal levels of immunocompetent cells.Our laboratory has shown that the Dahl S rat, when challenged with a high-salt diet, experiences both oxidative stress and inflammation (45), and this is associated with hypertension and considerable r...

Plasma Vitamin D Level and Change in Albuminuria and eGFR According to Sodium Intake

“…Increased renal ACE activity caused by high sodium intake combined with increased renin production caused by low vitamin D (24,37) may concertedly promote progression of albuminuria. Proinflammatory and profibrotic pathways could also underlie the interaction, because both vitamin D deficiency (25,(37)(38)(39) and high sodium intake (11,40,41) have been linked to increased renal inflammation and fibrosis.…”

P2X7 receptor antagonism attenuates the hypertension and renal injury in Dahl salt-sensitive rats

“…21,22 It is likely that a higher responsiveness of the P2X 7 pathway in the DS rats may aggravate inflammation in the kidney that has been damaged by hypertension. High-salt-containing diets in DS rats induced increased blood pressure, urinary protein excretion, renal interstitial fibrosis, macrophage infiltration and T-cell infiltration.…”

Lipid Peroxidation and Antioxidants in Arterial Hypertension

“…Prevented the development of hypertension induced by RAS activation [50] Transiently decreased blood pressure in Ang IIhypertensive rats [49] Reduced blood pressure in high-volume hypertension in mice [269] Lacked a sustained antihypertensive effect in Ang II-induced hypertension [49] Ebselen Attenuated the blood pressure rise induced by Ang II in mice overexpressing p22phox in vascular smooth muscle and in littermate control mice [270] Failed to prevent the development of hypertension induced by the blockade of nitric oxide synthesis [256] Vitamin C Prevented the progression of hypertension induced by salt administration in SHRSP and in SHR [229,271] Attenuated salt-induced hypertension [272,273] Failed to prevent adrenocorticotropic hormone-induced hypertension [274] Vitamin E Prevented the progression of hypertension induced by salt administration in SHRSP [229] Attenuated hypertension in young SHRSP [275] Attenuated salt-induced hypertension [273] Failed to prevent adrenocorticotropic hormone-induced hypertension [274] Lipoic acid Reduced blood pressure in SHR [276] Prevented fructose-induced hypertension [277] Prevented/attenuated salt-induced hypertension [278] Prevented mineralocorticoid-induced Drug Antihypertensive effect Lack of antihypertensive effect hypertension [279] …”