The role of oxidative stress in salt-induced hypertension (original) (raw)
Related papers
2010
High salt intake produces vascular changes that contribute to the development of hypertension in salt-sensitive individuals. Because reactive oxygen species play a role in the pathogenesis of cardiovascular diseases, we investigated whether oxidative stress contributes to salt-sensitive hypertension. Sprague-Dawley rats were divided in different groups and received tap water (vehicle), 30 mmol/L of L-buthionine sulfoximine ([BSO] an oxidant), high salt ([HS] 1% NaCl), and BSO plus HS without and with antioxidant tempol (1 mmol/L) in drinking water for 12 days. Compared with vehicle, BSO treatment caused oxidative stress and mild increase in blood pressure. Thoracic aortic rings from BSO-treated rats exhibited decreased response to endothelium-independent vasorelaxants. In HS-treated rats, the response to vasoactive agents, as well as blood pressure, was unaffected. Concomitant treatment of rats with BSO and HS produced a marked increase in blood pressure and a decreased response to both endothelium-dependent and endothelium-independent vasorelaxants with an increase in EC 50 . Incubation of aortic tissue from BSO-treated rats with sodium nitroprusside showed decreased cGMP accumulation, whereas HS rats had decreased basal NO synthase activity. Tempol decreased oxidative stress, normalized blood pressure, and restored NO signaling and responses to vasoactive compounds in BSO and BSO plus HS rats. We conclude that BSO increases oxidative stress and reduces NO signaling, whereas HS reduces NO levels by decreasing the NO synthase activity. These phenomena collectively result in reduced responsiveness to both endothelium -dependent and endothelium-independent vasorelaxants and may contribute to salt-sensitive hypertension. (Hypertension. 2007;49[part 2]:664-671.)
2016
Abstract—The balance between endothelial nitric oxide (NO) and angiotensin II (Ang II) maintains the homeostasis of the cardiovascular and renal systems. We tested the hypothesis that increased oxidant stress linked to a functional imbalance between NO and Ang II might play a central pathogenetic role in salt-sensitive (SS) hypertension. We studied Dahl SS (DS) rats during the prehypertensive (5 days) and hypertensive (12 weeks) phases of a high-salt (4 % NaCl) diet. Control rats received a normal-salt (0.5 % NaCl, [NS]) diet. Prehypertensive DS rats (systolic blood pressure [SBP] 1382 mm Hg) manifested a 35 % increase (P0.05) in aortic superoxide (O2–) production without evidence of end-organ damage. Hypertensive DS rats (SBP 21411 mm Hg) had impaired endothelium-dependent relaxation (EDR) and increased aortic O2 – production (320%), urinary isoprostane excretion (83%), aortic (20%) and left ventricular (LVH, 21%) hypertrophy, and proteinuria (124%). In prehypertensive DS rats, can...
American journal of hypertension, 2006
To examine the hypothesis that NAD(P)H oxidase (Nox)-derived superoxide generation is involved in the development of angiotensin II (ANG II)-induced hypertension, we evaluated the responses to ANG II infusion (65 ng/min; osmotic mini-pump) for 2 weeks in rats treated with or without apocynin (APO) (inhibitor of Nox subunits assembly) in drinking water (12 mmol/L). Rats were grouped according to their diets with varying salt content (normal salt [NS], 0.4%; high salt [HS], 8%; low salt [LS], 0.03%) given during the 2-week experimental period. The variation in salt intake did not alter mean arterial pressure (MAP, recorded via pre-implanted arterial catheter) but showed proportionate levels in urinary excretion rate of Isoprostaglandin(2alpha) (U(ISO)V; NS, 179 +/- 26; HS, 294 +/- 38; LS, 125 +/- 7 ng/kg/24 h). Treatment with ANG II increased MAP proportional to salt intake (NS, 126 +/- 3 to 160 +/- 5; HS, 116 +/- 4 to 184 +/- 5; LS, 125 +/- 1 to 154 +/- 5 mm Hg). However, ANG II incr...
Target for Oxidative Stress in Salt-Sensitive Hypertension
2014
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Hypertension, 2003
The balance between endothelial nitric oxide (NO) and angiotensin II (Ang II) maintains the homeostasis of the cardiovascular and renal systems. We tested the hypothesis that increased oxidant stress linked to a functional imbalance between NO and Ang II might play a central pathogenetic role in salt-sensitive (SS) hypertension. We studied Dahl SS (DS) rats during the prehypertensive (5 days) and hypertensive (12 weeks) phases of a high-salt (4% NaCl) diet. Control rats received a normal-salt (0.5% NaCl, [NS]) diet. Prehypertensive DS rats (systolic blood pressure [SBP] 138Ϯ2 mm Hg) manifested a 35% increase (PϽ0.05) in aortic superoxide (O 2 -) production without evidence of end-organ damage. Hypertensive DS rats (SBP 214Ϯ11 mm Hg) had impaired endothelium-dependent relaxation (EDR) and increased aortic O 2 production (320%), urinary isoprostane excretion (83%), aortic (20%) and left ventricular (LVH, 21%) hypertrophy, and proteinuria (124%). In prehypertensive DS rats, candesartan (10 mg · kg Ϫ1 · d Ϫ1 ) an Ang II type 1 receptor blocker (ARB), normalized O 2 production. In hypertensive DS rats, the ARB decreased aortic O 2 production by 71% and normalized EDR without affecting SBP (212Ϯ8 mm Hg), aortic hypertrophy, LVH, or proteinuria. Switching hypertensive DS rats to an NS diet did not affect SBP (208Ϯ8 mm Hg), LVH, aortic hypertrophy, or proteinuria and had minimal effects on O 2 and EDR. Concomitant ARB administration plus a switch to an NS diet normalized SBP (138Ϯ8 mm Hg) as well as end-organ damage. Dahl salt-resistant rats fed an HS diet for 12 weeks did not show hypertension or increased O 2 production. Thus, SS hypertension might represent a specific vascular diathesis linked to functional upregulation of Ang II action (increased O 2 synthesis) accompanied by insufficient NO bioavailability, which promotes severe endothelial dysfunction. (Hypertension. 2003;42:945-951.)
Interactions between oxidative stress and inflammation in salt-sensitive hypertension
AJP: Heart and Circulatory Physiology, 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-κB (NF-κB), 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 + 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 H2O2 and O2•− release and renal NF-κB. Antioxidant treatment with vitamins C and E in high-Na S rats also decreased renal monocytes/macrop...
Hypertension, 2005
This study was performed to examine the role of superoxide (O 2 Ϫ) in the development of salt sensitivity and hypertension induced by inhibition of nitric oxide (NO) generation. Male Sprague-Dawley rats were fed with diet containing either normal salt (NS) (0.4% NaCl) or high salt (HS) (4% NaCl). These rats were treated with or without an NO synthase inhibitor, nitro-L-arginine methylester (L-NAME) (15 mg/kg/d) and O 2 Ϫ scavenger, tempol (30 mg/kg per day) in the drinking water for 4 weeks. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and urine collection was performed during the course of experimental periods. At the end of 4 weeks, L-NAME treatment resulted in greater increases in SBP in HS rats (127Ϯ2 to 172Ϯ3 mm Hg; nϭ8) than in NS rats (130Ϯ2 to 156Ϯ2 mm Hg; nϭ9). Co-administration of tempol with L-NAME markedly attenuated these SBP responses to a similar level in both HS (128Ϯ3 to 147Ϯ2 mm Hg; nϭ8) and NS rats (126Ϯ2 to 142Ϯ3 mm Hg; nϭ8). Urinary 8-isoprostane excretion (U Iso V) increased in response to L-NAME treatment that was higher in HS (10.6Ϯ0.5 to 21.5Ϯ0.8 ng/d) than in NS rats (10.8Ϯ0.7 to 16.9Ϯ0.6 ng/d). Co-treatment with tempol completely abolished these U Iso V responses to L-NAME in both HS and NS rats but did not alter urinary H 2 O 2 excretion rate. The decreases in urinary nitrate/nitrite excretion in response to L-NAME treatment were not altered by co-administration of tempol in both HS and NS rats. These data suggest that enhancement of O 2 Ϫ activity during NO inhibition contributes to the development of salt sensitivity that is associated with NO-deficient hypertension. (Hypertension. 2005;46[part 2]:1026-1031.
Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity
American Journal of Physiology-renal Physiology, 2003
High-salt diet is known to induce or aggravate hypertension in animal models of hypertension and in humans. When Sprague-Dawley rats (n ϭ 60) are fed a moderately high-fat diet (32% kcal fat, 0.8% NaCl) for 10 wk, about one-half develop obesity [obesity prone (OP)] and mild hypertension, whereas the other half [obesity resistant (OR)] maintain body weight equivalent to a low-fat control (C) and are normotensive. The aim of this study was to test the effect of high-NaCl diets (2 and 4% NaCl) on the development of hypertension and obesity, oxidative stress, and renal function. Both 2 and 4% NaCl induced an early increase in systolic blood pressure of OP but not OR or C rats. High-salt intake induced an increase in the size and reduction in number of adipocytes, concomitant to a twofold increase in circulating leptin in OP rats. Aortic superoxide generation indicated a 2.8-fold increase in the OP high-salt vs. normalsalt groups, whereas urine isoprostanes were not significantly increased. Also, hydroxynonenal protein adducts in the kidney were highly increased in OP rats on 2 and 4% NaCl, indicating oxidative stress in the renal tissue. Urine albumin was increased threefold in the OP on 2% NaCl and fourfold in the same group on 4% NaCl vs. 0.8% NaCl. Kidney histology indicated a higher degree of glomerulosclerosis in OP rats on high-salt diets. In summary, high-salt diet accelerated the development but did not increase the severity of hypertension; high salt increased oxidative stress in the vasculature and kidney and induced kidney glomerulosclerosis and microalbuminuria. Also, the OP rats on high salt displayed adipocyte hypertrophy and increased leptin production.
Possible Mechanisms of Salt-Induced Hypertension in Dahl Salt-Sensitive Rats
Physiology & Behavior, 1998
Possible mechanisms of salt-induced hypertension in Dahl salt-sensitive rats. PHYSIOL BEHAV 65 (3) 563-568, 1998.-Genetic factors, diet, and salt sensitivity have all been implicated in hypertension. To further understand the mechanisms involved in salt-induced hypertension, cardiovascular, hemodynamics, and biochemical parameters in Dahl salt-sensitive rats were evaluated in animals on high-and lowsodium diets. During a 4-week treatment period, blood pressure was significantly elevated in the high (8.0%) salt group compared to the low (0.3%) salt group ( p р 0.05 for weeks 2 and 4, respectively). No significant changes were observed in heart rate. The increase in blood pressure was associated with significant increases in lower abdominal aortic and renal vascular resistance, along with a reduction in blood flow. A fourfold increase in arginine vasopressin was observed in animals on the high-salt diet. In contrast, there was no effect on plasma sodium, potassium, or aldosterone levels during the treatment period. As measured in isolated aortic rings, the high-salt diet also caused a significant elevation in stimulated norepinephrine release and a reduction in cyclic GMP levels. These data suggest that salt-induced elevation in blood pressure is due to activation of both the sympathetic and arginine vasopressin systems via mechanisms involving decreased cyclic GMP generation in vascular smooth muscle.
AJP: Renal Physiology, 2010
A deficiency in nitric oxide (NO) generation leads to salt-sensitive hypertension, but the role of increased superoxide (O2−) in such salt sensitivity has not been delineated. We examined the hypothesis that an enhancement in O2− activity induced by high-salt (HS) intake under deficient NO production contributes to the development of salt-sensitive hypertension. Endothelial NO synthase knockout (eNOS KO; total n = 64) and wild-type (WT; total n = 58) mice were given diets containing either normal (NS; 0.4%) or high-salt (HS; 4%) for 2 wk. During this period, mice were chronically treated with a O2− scavenger, tempol (400 mg/l), or an inhibitor of NADPH oxidase, apocynin (1 g/l), in drinking water or left untreated ( n = 6–8 per group). Blood pressure was measured by radiotelemetry and 24-h urine samples were collected in metabolic cages. Basal mean arterial pressure (MAP) in eNOS KO was higher (125 ± 4 vs. 106 ± 3 mmHg) compared with WT. Feeding HS diet did not alter MAP in WT but i...