Plasma zinc levels in nephrectomized and ureteral ligated rats.

The effect of nephrectomy and ureteral ligation on the plasma zinc levels of zinc-supplemented and unsupplemented rats was studied. Bilateral nephrectomy, and to a greater extent bilateral ureteral ligation, resulted in a significant lowering of plasma zinc in the unsupplemented rats. Sham operation caused a lesser but significant lowering of plasma zinc which was not different from the effect of unilateral nephrectomy or unilateral ureteral ligation. Adding zinc to the drinking fluid of the bilateral nephrectomized rats raised their plasma zinc levels to that of sham-operated controls, but had no effect on the plasma zinc levels of the bilateral ureteral-ligated rats.     

Splanchnic and systemic hemodynamic alterations in chronic, progressive portal hypertensive rats

Systemic and splanchnic hemodynamics were studied by using the radioactive microsphere technique, in rats in which a chronic and progressive portal or intrahepatic hypertension was produced by the placement of a nonconstricting, well fitted ligature around the portal or suprahepatic vein when the rat weighted about 100 g. The hemodynamic measurements were performed 80-90 days after ligature placement. Suprahepatic ligated rats presented portal and intrahepatic hypertension, but nonportal-systemic shunts (PSS). The only hemodynamic disturbance observed was a decrease in renal blood flow. Portal ligated rats showed a wide range of PSS and were divided in two subgroups. The subgroups with high PSS rate (greater than 10%) showed increased cardiac output and plasma renin content, as well as decreased splanchnic blood flow, portal venous inflow, hepatic blood flow and renal blood flow. Low portal-systemic shunts subgroups showed decreased cardiac output while its distribution was similar to the control rats. There was no correlation between portal pressure and shunt rate. Low shunt groups, furthermore, showed increased levels of plasma renin concentration.     

Action of arachidonic acid in ureteral-ligated kidney of the anesthetized canine: possible lipoxygenase activity

In anesthetized dogs 48 h after unilateral ureteral ligation, intra-arterial injection of arachidonic acid produced a transient increase followed by a prolonged decrease of resistance in the ureteral-ligated kidney; whereas, in the control kidney, only the prolonged decrease in resistance was observed in response to arachidonate. Indomethacin blocked not only the arachidonate-induced renal efflux of both immunoreactive 6-keto-prostaglandin F1 alpha and thromboxane B2 but also vasodilation in both kidneys. In contrast, the initial vasoconstriction in the obstructed kidney was not affected by pretreatment with the cyclo-oxygenase inhibitor. Infusion of 5,8,11,14-eicosatetraynoic acid, an inhibitor of lipoxygenase activity, into the ureteral-ligated kidney after indomethacin markedly reduced the initial vasoconstrictor response to arachidonate. These data demonstrate that vascular reactivity to arachidonic acid is altered in the ureteral-obstructed kidney and are consistent with the hypothesis that formation of lipoxygenase as well as cyclooxygenase derivatives may participate in the hemodynamic responses to arachidonic acid in this pathophysiologic model.     

Changes in kidney tissue and effects of erythropoietin after acute heart failure

Impairment of cardiac function causes renal damage. Renal failure after heart failure is attributed to hemodynamic derangement including reduced renal perfusion and increased venous pressure. One mechanism involves apoptosis and is defined as cardiorenal syndrome type 1. Erythropoietin (EPO) is a cytokine that induces erythropoiesis under hypoxic conditions. Hypoxia inducible factor 1 alpha (HIF-1α) plays a regulatory role in cellular response to hypoxia. Protective effects of EPO on heart, kidney and nervous system are unrelated to red blood cell production. We investigated early changes in and effects of EPO on renal tissues of rats with myocardial infarction by morphology and immunohistochemistry. Coronary artery ligation was used to induce myocardial infarction in Wistar rats. Group 1 comprised sham operated rats; groups 2, 3 and 4 included rats after coronary artery ligation that were sacrificed 6 h after ligation and that were treated with saline, 5,000 U/kg EPO or 10,000 U/kg EPO, respectively; group 5 included rats sacrificed 1 h after ligation. Group 2 showed increased renal tubule damage. Significantly less tubule damage was observed in EPO treated groups. EPO and EPO receptor (EPO-R) immunostaining intensities increased slightly for group 5 and became more intense for group 2. EPO and EPO-R immunostaining was observed in the interstitial area, glomerular cells and tubule epithelial cells of EPO treated groups. HIF-1α immunostaining was observed in collecting tubules in the medulla only in group 2. Caspase-3 immunostaining is an indicator of apoptosis. Caspase-3 staining intensity decreased in renal medulla of EPO treated groups. EPO treatment may exert a protective effect on the renal tissues of patients with cardiorenal syndrome.     

The effect of pancreatic and intestinal venous blood on hepatic atrophy and compensatory hyperplasia in the rat

Hepatotrophic effect of pancreatic and intestinal venous blood was studied in rats with mesocaval or distal splenocaval shunt following ligation of a branch of the portal vein supplying 70% of liver mass. Because 2/3 of liver mass was deprived of portal flow the nonligated liver lobes were not hypoperfused due to shunt procedure. During the first three postoperative days the DNA synthesis, mitotic index, and changes in relative weights were measured in both ligated (atrophied) and nonligated (compensatory hyperplasia) parts of the liver. It was found, that the restorative capacity of the liver existed in rats with selective portasystemic shunts. The stimulus to growth was greater in lobes supplied by intestinal venous blood compared to those perfused by pancreatic effluent. The increase in DNA synthesis occurred in lobes undergoing atrophy and the intensity of this response was also dependent on type of shunt since recirculation of intestinal blood by way of the hepatic artery inhibited atrophy to a greater extent than pancreatic venous effluent. Although the patency of arterial branches was confirmed the ligated lobes showed necrotic lesions. Systemic recirculation of intestinal venous blood far more inhibited necrosis than pancreatic venous blood.     

Blockade of brain mineralocorticoid receptors or Na+ channels prevents sympathetic hyperactivity and improves cardiac function in rats post-MI

In rats post-myocardial infarction (MI), sympathetic hyperactivity can be prevented by blockade of brain mineralocorticoid receptors (MR). Stimulatory responses to central infusion of aldosterone can be blocked by benzamil and therefore appear to be mediated via Na+ channels, presumably epithelial Na+ channels (ENaC), in the brain. To evaluate this concept of endogenous mineralocorticoids in Wistar rats post-MI, we examined effects of blockade of MR and Na+ channels in the brain. At 3 days after coronary artery ligation, intracerebroventricular infusions were started with spironolactone (400 ng.kg(-1).h(-1)) or its vehicle, or with benzamil (4 microg.kg(-1).h(-1)) or its vehicle, using osmotic minipumps. Rats with sham ligation served as control. After 4 wk, in conscious rats, mean arterial pressure, heart rate, and renal sympathetic nerve activity were recorded at rest and in response to air-jet stress, intracerebroventricular injection of the alpha2-adrenoceptor agonist guanabenz, and intravenous infusion of phenylephrine and nitroprusside for baroreflex function. MI size was similar among the four groups of rats (approximately 31%). In rats treated post-MI with vehicles, cardiac function was decreased, sympathetic reactivity was enhanced, and baroreflex function was impaired. Blockade of brain Na+ channels or brain MR similarly prevented sympathetic hyperactivity and impairment of baroreflex function and improved cardiac function. These findings suggest that in rats post-MI, increased binding of endogenous agonists to MR increases ENaC activity in the brain and thereby leads to sympathetic hyperactivity and progressive left ventricular dysfunction.     

Asymmetrical dimethylarginine plasma clearance persists after acute total nephrectomy in rats

Elevated plasma concentrations of symmetrical dimethylarginine (SDMA) and asymmetrical dimethylarginine (ADMA) are repeatedly associated with kidney failure. Both ADMA and SDMA can be excreted in urine. We tested whether renal excretion is necessary for acute, short-term maintenance of plasma ADMA and SDMA. Sprague-Dawley rats underwent sham operation, bilateral nephrectomy (NPX), ureteral ligation, or ureteral section under isoflurane anesthesia. Tail-snip blood samples (250 microl) were taken before and at 6- or 12-h intervals for 72 h after operation. Plasma clearance was assessed in intact and NPX rats. High-performance liquid chromatography determined SDMA and ADMA concentrations. Sodium, potassium, creatinine, blood urea nitrogen (BUN), and body weight were also measured. Forty-eight hours after NPX, SDMA increased 25 times (0.23 +/- 0.03 to 5.68 +/- 0.30 microM), whereas ADMA decreased (1.17 +/- 0.08 to 0.73 +/- 0.08 microM) by 38%. Creatinine and BUN increased, paralleling SDMA. Sham-operated animals showed no significant changes. Increased SDMA confirms continuous systemic production of SDMA and its obligatory renal excretion, much like creatinine. In contrast, decreased plasma ADMA suggests that acute total NPX either reduced systemic ADMA formation and/or systemic hydrolysis of ADMA increased 48-h post-NPX. However, plasma clearance of ADMA appeared unchanged 48 h after NPX. We conclude that renal excretory function is needed for SDMA elimination but not needed for acute, short-term ADMA elimination in that systemic hydrolysis is fully capable of clearing plasma ADMA.     

Tissue engineering skin flaps: which vascular carrier, arteriovenous shunt loop or arteriovenous bundle, has more potential for angiogenesis and tissue generation?

This study was designed to clarify which vascular carrier, the arteriovenous shunt loop or the arteriovenous bundle, has more potential as a vascular carrier for an artificial skin flap in rats. An arteriovenous shunt loop was constructed between the femoral artery and vein using an interpositional artery (group I) or vein (group II) graft. For arteriovenous bundle groups, the femoral artery and vein were used and subdivided into two groups: distal ligation type (group III) and flow-through type (group IV). The vascular pedicle was wrapped with an artificial dermis and implanted beneath the inguinal skin for 4 weeks. For the control group, a folded sheet of artificial dermis without any vascular carrier was embedded. In experiment 1, the volumes of generated tissue within the artificial dermis were measured in the experimental and control groups (n = 5 in each group). In experiment 2, the origin of new blood vessels sprouting from the arteriovenous shunt loop and arteriovenous bundle were evaluated histologically. The volume of generated tissue in the shunt groups was significantly greater than that in the bundle groups (p < 0.01). However, the bundle groups also showed a great potential for producing new tissue. Serial histological studies showed that new capillaries were derived not only from the vasa vasorum of the femoral vessels but directly from the femoral vein in both the shunt and the bundle groups. This "sprouting" was extensively exhibited in the group III. Although the arteriovenous shunt loop showed a greater potential for producing new tissue and capillaries, the distal ligation type of bundle was thought to be an effective and practical vascular carrier for producing a tissue-engineered skin flap.     

Renorenal reflexes: neural and functional responses

Evidence supporting the existence of renorenal reflexes is reviewed. Renal mechanoreceptors (MR) and afferent renal nerve fibers are localized in the corticomedullary region and in the wall of the renal pelvis. Stimulating renal MR by increased ureteral pressure (increases UP) or increased renal venous pressure (increases RVP) and renal chemoreceptors (CR) by retrograde ureteropelvic perfusion with 0.9 M NaCl results in increased ipsilateral afferent renal nerve activity (ARNA) in a variety of species. However, renorenal reflex responses to renal MR and CR differ among species. In the dog, stimulating renal MR results in a modest contralateral excitatory renorenal reflex response with contralateral renal vasoconstriction that is integrated at the supraspinal level. Renal CR stimulation is without effect on systemic and renal function. However, in the rat the responses to renal MR and CR stimulation are opposite to those of the dog. Increased ureteral pressure, renal venous pressure, or retrograde ureteropelvic perfusion with 0.9 M NaCl each results in a receptor-specific contralateral inhibitory renorenal reflex response. The afferent limb consists of increased ipsilateral ARNA and the efferent limb of decreased contralateral efferent RNA with contralateral diuresis and natriuresis. The renorenal reflex responses to MR and CR stimulation are integrated at the supraspinal level.     

Increased expression of renal neutral endopeptidase in severe heart failure

The enzyme neutral endopeptidase (NEP; EC 3.4.24.11) cleaves several vasoactive peptides such as the atrial natriuretic peptide (ANP). ANP is a hormone of cardiac origin with diuretic and natriuretic actions. Despite elevated circulating levels of ANP, congestive heart failure (CHF) is characterized by progressive sodium and water retention. In order to elucidate the loss of natriuretic and diuretic properties of ANP in CHF we analyzed activity, protein concentrations, mRNA and immunostaining of NEP in kidneys of different models of severe CHF in the rat.CHF was induced by either aortocaval shunt, aortic banding or myocardial infarction in the rat. All models were defined by increased left ventricular end-diastolic pressure and decreased contractility. The diminished effectiveness of ANP was reflected by reduced cGMP/ANP ratio in animals with shunt or infarction.Renal NEP activity was increased in rats with aortocaval shunt (203 +/- 7%, p < 0.001), aortic banding (184 +/- 11%, p < 0.001) and infarction (149 +/- 10%, p < 0.005). Western blot analysis revealed a significant increase in renal NEP protein content in two models of CHF (shunt: 214 +/- 57%, p < 0.05; infarction: 310 +/- 53 %, p < 0.01). The elevated protein expression was paralleled by a threefold increase in renal NEP-mRNA level in the infarction model.The increased renal NEP protein expression and activity may lead to enhanced degradation of ANP and may contribute to the decreased renal response to ANP in heart failure. Thus, the capacity to counteract sodium and water retention, would be diminished. The increased renal NEP activity may therefore be a hitherto unknown factor in the progression of CHF.     

Prostaglandins and renal function II. The effect of prostaglandin inhibition on autoregulation of blood flow in the intact kidney of the dog

In order to evaluate the effect of prostaglandin release on renal autoregulation in the intact kidney of the dog, pressure-flow curves were obtained before and after the administration of either indomethacin or meclofenamate, two potent prostaglandin synthetase inhibitors. After drug administration renal venous prostaglandin E decreased in each of eight studies with a mean change from 286 to 141 pg/ml (p < .001). In addition, prostaglandin inhibition was associated with a 31 percent decrease in renal blood flow and a 58 percent increase in renal resistance. Yet, as renal perfusion pressure was decreased by aortic constriction, the change in flow per pressure reduction and the percent change in renal resistance were not significantly different after prostaglandin inhibition when compared to control values in the same animals. The magnitude of the pressure range over which autoregulation was maintained was also similar in the two groups although both the initial and lowest level of autoregulation were slightly higher after prostaglandin inhibition. It is concluded that the administration of these prostaglandin synthetase inhibitors does not significantly impair renal autoregulation in the intact dog kidney.     

Differential regulation of cardiac ANP and BNP mRNA in different stages of experimental heart failure

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones that are involved in water and electrolyte homeostasis in heart failure. Although both hormones exert almost identical biological actions, the differential regulation of cardiac ANP and BNP mRNA in compensated and overt heart failure is not known. To study the hypothesis that cardiac BNP is more specifically induced in overt heart failure, a large aortocaval shunt of 30 days duration was produced in rats and compared with compensated heart failure. Compensated heart failure was induced either by a small shunt of 30 days duration or by a large shunt of 3 days duration. Both heart failure models were characterized by increased cardiac weight, which was significantly higher in the large-shunt model, and central venous pressure. Left ventricular end-diastolic pressure was elevated only in the overt heart failure group (control: 5.7 +/- 0. 7; small shunt: 8.6 +/- 0.9; large shunt 3 days: 8.5 +/- 1.7; large shunt 30 days: 15.9 +/- 2.6 mmHg; P < 0.01). ANP and BNP plasma concentrations were elevated in both heart failure models. In compensated heart failure, ANP mRNA expression was induced in both ventricles. In contrast, ventricular BNP mRNA expression was not upregulated in any of the compensated heart failure models, whereas it increased in overt heart failure (left ventricle: 359 +/- 104% of control, P < 0.001; right ventricle: 237 +/- 33%, P < 0.01). A similar pattern of mRNA regulation was observed in the atria. These data indicate that, in contrast to ANP, cardiac BNP mRNA expression might be induced specifically in overt heart failure, pointing toward the possible role of BNP as a marker of the transition from compensated to overt heart failure.     

在大鼠牵拉心房和急性扩张血容量所致的肾效应

在28只麻醉大鼠,观察了牵拉心房和急性扩容时的肾效应。用5—7g的砝码牵拉大鼠右心房30min(n=6)时,尿量、尿钠和尿钾分别增加98％、127％和59％;牵拉左心房(n=4)所致的肾效应与牵拉右心房的基本相同。切断双侧迷走神经后,牵拉右心房的肾效应无明显改变。在切断迷走神经的大鼠,观察了双线结扎右心耳对急性扩容后肾效应的影响。急性扩容在假手术大鼠引起明显的利尿、钠尿和钾尿效应(P<0.01);而结扎右心耳的大鼠,钠尿效应约为假手术大鼠的一半,但尿量和尿钾排泄量与假手术组无明显异差。上述肾效应不受切断迷走神经的影响,因此不是通过容量感受性反射引起的。根据以上结果,我们推测,牵拉心房或急性扩容引起的尿量、尿铜和尿钾的增多,可能是心房钠尿因子释放增多所致,而结扎右心耳则导致释放入血流的心房钠尿因子减少。     

Regulation of atrial contraction by PKA and PKC during development and regression of eccentric cardiac hypertrophy

ANG II plays a major role in development of cardiac hypertrophy through its AT1 receptor subtype, whereas angiotensin-converting enzyme (ACE) inhibitors are effective in reversing effects of ANG II on the heart. The objective of this study was to investigate the role of PKA and PKC in the contractile response of atrial tissue during development and ACE inhibitor-induced regression of eccentric hypertrophy induced by aortocaval shunt. At 1 wk after surgery, sham and shunt rats were divided into captopril-treated and untreated groups for 2 wk. Then isometric contraction was assessed by electrical stimulation of isolated rat left atrial preparations superfused with Tyrode solution in the presence or absence of specific inhibitors KT-5720 (for PKA) and Ro-32-0432 (for PKC) and high Ca2+. Peak tension developed was greater in shunt than in sham hearts. However, when expressed relative to tissue mass, hypertrophied muscle showed weaker contraction than muscle from sham rats. In sham rats, peak tension developed was more affected by PKC than by PKA inhibition, whereas this differential effect was reduced in the hypertrophied heart. Treatment of shunt rats with captopril regressed left atrial hypertrophy by 67% and restored PKC-PKA differential responsiveness toward sham levels. In the hypertrophied left atria, there was an increase in the velocity of contraction and relaxation that was not evident when expressed in specific relative terms. Treatment with ACE inhibitor increased the specific velocity of contraction, as well as its PKC sensitivity, in shunt rats. We conclude that ACE inhibition during eccentric cardiac hypertrophy produces a negative trophic and a positive inotropic effect, mainly through a PKC-dependent mechanism.     

Effects of administration of tri-iodothyronine on the response of cardiac and renal pyruvate dehydrogenase complex to starvation for 48 h.

Effects of administration of tri-iodothyronine (T3) on activities of cardiac and renal pyruvate dehydrogenase complex (active form, PDHa) were investigated. In fed rats, T3 treatment did not affect cardiac or renal PDHa activity, although blood non-esterified fatty acid and ketone-body concentrations were increased. Starvation (48 h) of both control and T3-treated rats resulted in similar increases in the steady-state concentrations of fatty acids and ketone bodies, but inactivation of cardiac and renal pyruvate dehydrogenase complex activities was diminished by T3 treatment. Inhibition of lipolysis increased renal and cardiac PDHa in control but not in T3-treated 48 h-starved rats, despite decreased fatty acid and ketone-body concentrations in both groups. The results suggest that hyperthyroidism influences the response of cardiac and renal PDHa activities to starvation through changes in the metabolism of lipid fuels in these tissues.     

Splenic reflex modulation of central cardiovascular regulatory pathways

The splenorenal reflex induces changes in mean arterial pressure (MAP) and renal function. We hypothesized that, in addition to spinal pathways previously identified, these effects are also mediated through central pathways. We investigated the effect of elevated splenic venous pressure on central neural activation in intact, renal-denervated, and renal + splenic-denervated rats. Fos-labeled neurons were quantified in the nucleus of the tractus solitarius (NTS), paraventricular nucleus (PVN), supraoptic nucleus (SON), and subfornical organ (SFO) after 1-h partial splenic vein occlusion (SVO) in conscious rats bearing balloon occluders around the splenic vein, telemetric pressure transducers in the gastric vein (splenic venous pressure), and abdominal aorta catheters (MAP). SVO stimulated Fos expression in the PVN and SON, but not NTS or SFO of intact rats. Renal denervation abolished this response in the parvocellular PVN, while renal + splenic denervation abolished activation in the magnocellular PVN and the SON. In renal-denervated animals, SVO depressed Fos expression in the NTS and increased expression in the SFO, responses that were abolished by renal + splenic denervation. In intact rats, SVO also induced a fall in right atrial pressure, an increase in renal afferent nerve activity, and an increase in MAP. We conclude that elevated splenic venous pressure does induce hypothalamic activation and that this is mediated through both splenic and renal afferent nerves. However, in the absence of renal afferent input, SVO depressed NTS activation, probably as a result of the accompanying fall in cardiac preload and reduced afferent signaling from the cardiopulmonary receptors.     

Role of Nox4 in murine models of kidney disease

Nox4 is a hydrogen peroxide-producing NADPH oxidase highly expressed in the kidney which has been linked to epithelial cell injury and diabetic-induced cellular dysfunction in cultured cells. The role of the enzyme for renal pathology in vivo, however, is unclear. To address this, three experimental animal models of renal injury (streptozotocin diabetes I, unilateral ureteral ligation (UUO), and 5/6 nephrectomy (5/6Nx)) were studied in either Nox4-inducible (Nox4(?/?)) or constitutive knockout (Nox4(-/-)) mice. Nox4 contributed more than 80% of diphenylene iodonium-sensitive H(2)O(2) formation of freshly isolated tubules determined by Amplex Red assay. In streptozotocin diabetes, acute deletion of Nox4 by tamoxifen-activated cre-recombinase increased albuminuria, whereas matrix deposition was similar between WT and Nox4(?/?) mice. Interestingly, renal Nox4 expression, mainly localized to tubular cells, decreased in the course of diabetes and this was not associated with a compensatory upregulation of Nox1 or Nox2. In the UUO model, renal expression of ICAM1, connective tissue growth factor, and fibronectin were higher in kidneys of Nox4(?/?) than control mice. Also in this model, levels of Nox4 decreased in the course of the disease. In the 5/6Nx model, which was performed in SV129 and SV129-Nox4(-/-) mice, no difference in the development of hypertension and albuminuria was found between the strains. Collectively, the first in vivo data of the kidney do not support the view that Nox4 is a main driver of renal disease. It rather appears that under specific conditions Nox4 may even slightly limit injury and disease progression.     

Renal catabolism of human glucagon-like peptides 1 and 2

The renal catabolism of [125I]glucagon-like peptide 1 (GLP-1) and [125I]glucagon-like peptide 2 (GLP-2) has been studied both in vivo, by the disappearance of these peptides from the plasma of bilaterally nephrectomized (BNX), ureteral-ligated (BUL) or normal rats, and in vitro, analyzing their catabolism by the isolated, perfused rat kidney. Results from in vivo studies demonstrated that half-disappearance time for both peptides was lower in controls than in BUL rats, and this value in BUL rats was not significantly different from that in BNX rats. In addition, metabolic clearance rate of GLP-1 was higher in control rats than in the other two groups of animals. Urinary clearance rate of both peptides was negligible. In isolated kidney experiments, values for organ clearance of both [125I]GLP-1 and [125I]GLP-2 were similar to those of inulin clearance, which represents the glomerular filtration rate. Urinary clearance of trichloroacetic acid precipitable radioactivity represented less than 1% of total clearance. In conclusion, these results demonstrate a significant role for the kidney in the plasma removal of [125I]GLP-1 and [125I]GLP-2 by a mechanism that involves glomerular filtration and tubular catabolism.     

Interactions between oxidative stress and inflammation in salt-sensitive hypertension

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-kappaB (NF-kappaB), 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 H(2)O(2) and O(2)(*-) release and renal NF-kappaB. 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-alpha 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-kappaB, and arterial pressure and improved renal function and damage.