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Pathophysiological states, including cardiovascular and renal diseases, are characterized by oxidative stress but what is less clear is whether physiological challenges incur a degree of altered oxidative metabolism. To this end, this study examined whether exposure to a high dietary sodium intake could cause an oxidative stress at the kidney. Animals, placed on either 0.3% or 3% sodium diets for 2 wk, were given a lethal dose of anesthetic, and kidneys were removed to analyze both NAD(P)H oxidase (NOX) and superoxide dismutase (SOD) expression and activities in the cortex and medulla. Placing animals on the high-sodium diet raised sodium and water excretion and caused an ~14-fold increase in urinary excretion of 8-isoprostane, a marker of oxidative stress, which was attenuated by chronic treatment with apocynin to prevent NAD(P)H oxidase activity. The protein expression of the NAD(P)H oxidase subunits NOX2 and p47phox and overall NAD(P)H oxidase activity were approximately doubled in the cortex of the rats on the high-sodium diet compared with those on the normal sodium intake while both SOD activity and expression were unchanged. By contrast, neither NOX nor SOD protein expression or activity were altered in the medulla when the rats were placed on the high-sodium intake. These data suggest that an elevation in dietary sodium intake can lead to increased generation of reactive oxygen species and a state of oxidative stress in the cortex but not to such a degree that it extends to the medulla. renal cortex; renal medulla; oxidative stress; nicotinamide adenine dinucleotide phosphate oxidase; superoxide dismutase doi: 10.1152/ajpregu.00541.2009.

It was hypothesized that renal sympathetic nerve activity (RSNA) and neuronal nitric oxide synthase (nNOS) are involved in the acute inhibition of renin secretion and the natriuresis following slow NaCl loading (NaLoad) and that RSNA participates in the regulation of arterial blood pressure (MABP). This was tested by NaLoad after chronic renal denervation with and without inhibition of nNOS by S-methyl-thiocitrulline (SMTC). In addition, the acute effects of renal denervation on MABP and sodium balance were assessed. Rats were investigated in the conscious, catheterized state, in metabolic cages, and acutely during anesthesia. NaLoad was performed over 2 h by intravenous infusion of hypertonic solution (50 [micro]mol*[min.sup.-1]*kg body [mass.sup.-1]) at constant body volume conditions. SMTC was coinfused in amounts (20 [micro]g*[min.sup.-1]*[kg.sup-1]) reported to selectively inhibit nNOS . Directly measured MABPs of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P < 0.005). Plasma renin concentration (PRC) was reduced by renal denervation (14.5 [+ or -] 0.2 vs. 19.3 [+ or -] 1.3 mIU/l, P < 0.005) and by nNOS inhibition (12.4 [+ or -] 2.3 vs. 19.6 [+ or -] 1.6 mlU/l, P < 0.005). NaLoad reduced PRC (P < 0.05) and elevated MABP modestly (P < 0.05) and increased sodium excretion six-fold, irrespective of renal denervation and SMTC. The metabolic data demonstrated that renal denervation lowered sodium balance during the first days after denervation (P < 0.001). These data show that renal denervation decreases MABP and renin secretion. However, neither renal denervation nor nNOS inhibition affects either the renin downregulation or the natriuretic response to acute sodium loading. Acute sodium-driven renin regulation seems independent of RSNA and nNOS under the present conditions. plasma renin concentration; total body sodium; blood pressure; sodium excretion

The processes involved in the renal damage resulting from ischemia-reperfusion injury are poorly understood. This study examined the contribution of prostaglandins and nitric oxide (NO) in the vascular responses to ischemia-reperfusion injury in the kidneys of normotensive and hypertensive rats. Groups of Wistar and stroke-prone spontaneously hypertensive rats (SHRSP) were dosed with polyethylene glycol vehicle, aspirin (53.5 mg x [kg.sup.-1] x [day.sup.-1]), NO-aspirin (100 mg x [kg.sup.-1] x [day.sup.-1]), or celecoxib (10 mg x [kg.sup.-1] x [day.sup.-1]) for 7 days. On day 7, rats were anesthetized with chloralose/urethane and the left kidney was exposed to a 30-min period of ischemia followed by 90-rain reperfusion. Renal cortical and medullary perfusions were monitored throughout using laser-Doppler flowmetry. In the vehicle- and celecoxib-treated Wistar rats, cortical and medullary postischemic perfusion was reduced to 66 and 62% and 53 and 62%, respectively (all P < 0.05), of baseline. The ischemia-induced reductions in cortical and medullary flux were ameliorated in the aspirin and NO-aspirin groups where flux fell to 96 and 78% and 105 and 83%, respectively (P < 0.05). There was a fall in cortical and medullary flux in the postischemic period in the vehicle-treated SHRSP to 82 and 77% (P < 0.05). These findings show that nonselective cyclooxygenase (COX) inhibition, and to an even greater extent NO donation, provided protection to the renal vasculature from ischemic injury in the Wistar rat but not in the SHRSP. This would suggest that prostaglandins are less important in the development of renal ischemia-reperfusion injury during hypertension and both COX isoforms must be inhibited to offset the decrease in renal hemodynamics. NO-NSAIDs; hypertension

The dependence of the response of the kidneys in terms of hemodynamics and tubular function to somatosensory stimulation on the renal nerve is investigated in anesthetized rats with intact or resected renal nerves stimulated with subcutaneous injection of capsaicin. The pressor and antinatriuresis response was abolished in subjects with resected renal nerves.

The magnitude and pattern of the renal sympathetic nerve activity responses and the functional correlates were compared to two distinct cases in hypertensive and normotensive rats by subcutaneously treating the rodents with capsaicin. Both the exposure to poisonous fumes and the administration of capsaicin had caused the stimulation of the somatosensory system, which led to the increase in blood pressure. The changes in renal hemodynamics and decreased water and sodium excretion were all found to be minimal.

The role of vagal function in the modulation of somatosensory-induced alterations in the power spectral pattern of renal nerve activity was analyzed in spontaneously hypertensive (SHR) and normotensive Wistar rats. Administration of capsaicin increased renal nerve activity and elevated blood pressure in SHR and normotensive Wistar rats. However, renal nerve activity in SHR rats were higher after capsaicin treatments compared to normotensive Wistar rats due to major deficiencies in vagal influence on the renal sympathetic nerve output.

Left renal nerves of rats were stimulated electrically to lower renal blood flow by 15, 30 and 45%, and the level of mRNA for renin and angiotensinogen were measured to evaluate the effect of short spells of nerve stimulation on renin and angiotensinogen expression within the kidney. While 1 hour stimulations led to a proportional decrease in sodium extraction and increase in plasma renin activity, stimulations for a longer period were required to enhance renal renin mRNA levels. A minimal enhancement of angiotensinogen mRNA level and low rates of nerve activity were observed.

Wu, Xiao Chun, Peter J. Harris, and Edward J. Johns. Nitric oxide and renal nerve-mediated proximal tubular reabsorption in normotensive and hypertensive rats. Am. J. Physiol. 277 (Renal Physiol. 46): F560-F566, 1999.--In Inactin-anesthetized Wistar rats with an intact renal innervation, intratubular nitro-L-arginine methyl ester (L-NAME, [10.sup.-4] M) increased proximal fluid uptake ([J.sub.va], at 2.47 [+ or -] 0.61 x [10.sup.-4] [mm.sup.3] [multiplied by] [mm.sup.-2] [multiplied by] [s.sup.-1]) by 17% (P [is less than] 0.05), whereas coadministration with sodium nitroprusside (SNP, [10.sup.-4] M) decreased [J.sub.va] by 18% (P [is less than] 0.01). Similar manipulation of NO generation was without effect in groups of Wistar rats subjected to acute renal denervation. Intratubular aminoguanidine ([10.sup.-4] M), a selective inducible nitric oxide synthase (NOS) blocker, had no effect on [J.sub.va] in intact kidneys of Wistar rats, but the neuronal NOS (nNOS) blocker, 7-nitroindazole ([10.sub.-4] M and [10.sup.-6] M) increased [J.sub.va] by 19-23% (both P [is less than] 0.001). In stroke-prone spontaneously hypertensive rats (SHRSP), [J.sub.va] values in the innervated kidneys were lower (P [is less than] 0.05) than in the corresponding Wistar groups and were unchanged by intratubular L-NAME or L-NAME plus SNP. The tonic attenuation of proximal epithelial transport by NO was dependent on the renal sympathetic nerves and appeared to be generated by the nNOS isoform of the enzyme. This role of NO was not evident in the SHRSP. nitric oxide synthase; renal sympathetic nerves; proximal tubular sodium reabsorption; stroke-prone spontaneously hypertensive rats

Examines the renal nerve-dependent renal hemodynamic and tubular responses to somatosensory stimulation in the anesthetized rat by use of subcutaneously applied capsaicin when the action of angiotensin G (ANG) III was blocked peripherally or selectively within the brain. Increase in blood pressure upon activation of skin somatosensory receptors; Blockage of the reductions in urine flow and sodium excretion.

The article reviews the article about the role of adrenergic on the development of renin cells in nephrogenesis.

Angiotensin II at the kidney regulates renal hemodynamic and excretory function, but the actions of an alternative metabolite, angiotensin (1-7), are less clear. This study investigated how manipulation of dietary sodium intake influenced the renal hemodynamic and excretory responses to intrarenal administration of angiotensin (1-7). Renal interstitial infusion of angiotensin (1-7) in anesthetized rats fed a normal salt intake had minimal effects on glomerular filtration rate but caused dose-related increases in urine flow and absolute and fractional sodium excretions ranging from 150 to 200%. In rats maintained for 2 wk on a low-sodium diet angiotensin (1-7) increased glomerular filtration rate by some 45%, but the diuretic and natriuretic responses were enhanced compared with those in rats on a normal sodium intake. By contrast, renal interstitial infusion of angiotensin (1-7) in rats maintained on a high-sodium intake had no effect on glomerular filtration rate, whereas the diuresis and natriuresis was markedly attenuated compared with those in rats fed either a normal or low-sodium diet. Plasma renin and angiotensin (1-7) were highest in the rats on the low-sodium diet and depressed in the rats on a high-sodium diet. These findings demonstrate that the renal hemodynamic and excretory responses to locally administered angiotensin (1-7) is dependent on the level of sodium intake and indirectly on the degree of activation of the renin-angiotensin system. The exact way in which angiotensin (1-7) exerts its effects may be dependent on the prevailing levels of angiotensin II and its receptor expression.

There is evidence that in cardiac failure, there is defective baroreceptor reflex control of sympathetic nerve activity. Often, cardiac failure is preceded by a state of cardiac hypertrophy in which there may be enhanced performance of the heart. This study investigated whether in two different models of cardiac hypertrophy, there was an increased contribution of nitric oxide (NO) to the low-pressure baroreceptor regulation of renal sympathetic nerve activity (RSNA) and nerve-dependent excretory function. Administration of a volume load, 0.25* body wt/min saline for 30 min, in normal rats decreased RSNA by 40* and increased urine flow by some 9-fold. Following nitro-L-arginine methyl ester (L-NAME) administration, 10 μg·kg(-1)·min(-1) for 60 min, which had no effect on blood pressure, heart rate, or RSNA, the volume load-induced renal sympathoinhibitory and excretory responses were markedly enhanced. In cardiac hypertrophy states induced by 2 wk of isoprenaline/caffeine or 1 wk thyroxine administration, the volume challenge failed to suppress RSNA, and there were blunted increases in urine flow in the innervated kidneys, but following L-NAME infusion, the volume load decreased RSNA by 30-40* and increased urine flow by some 20-fold in the innervated kidneys, roughly to the same extent as observed in normal rats. These findings suggest that the blunted renal sympathoinhibition and nerve-dependent diuresis to the volume load in cardiac hypertrophy are related to a heightened production or activity of NO within either the afferent or central arms of the reflex.