scholarly journals Development of salt-sensitive hypertension in a sensory denervated model: the underlying mechanisms

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S125-S129 ◽  
Author(s):  
Donna H Wang ◽  
Yan Huang
Keyword(s):  
Renal Cortex ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Male Rats ◽  
At2 Receptor ◽  
Ang Ii ◽  
High Sodium ◽  
Sodium Diet ◽  
Salt Sensitive Hypertension ◽  
High Sodium Diet

We use a novel salt-sensitive hypertensive model recently developed in our laboratory. This model shows that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to a salt load with a significant rise in blood pressure (BP). To test the hypothesis that development of salt-sensitive hypertension in sensory denervated rats is mediated by abnormal regulation of both circulating and tissue renin-angiotensin systems (RAS), neonatal Wistar rats were given capsaicin, 50 mg/kg s.c., on the first and second days of life. Control rats were treated with vehicle solution. After the weaning period, male rats were divided into four groups and subjected to the following treatments for three weeks: control + high sodium diet (4%, CON-HS), capsaicin pretreatment + normal sodium diet (0.5%, CAP-NS), capsaicin pretreatment + high sodium diet (CAP-HS), and capsaicin pretreatment + high sodium diet + candesartan cilexetil (10 mg/kg/per day, CAP-HS-CAN). Radioimmunoassay shows that plasma renin activity (ng/ml/hr, PRA) was higher in CAP-NS (2.58±0.17) than in CON-HS (0.14±0.03) and CAP-HS (0.74±0.15), and it was higher in CAP-HS than in CON-HS (p<0.05). Western blot analysis shows that expression of the angiotensin II (Ang II) type 1 (AT1) receptor in both the renal cortex and outer medulla was higher in CAP-HS than in CON-HS and CAP-NS rats (p<0.05). Expression of the Ang II type 2 (AT2) receptor in the renal cortex was higher in both CAP-HS and CAP-NS than in CON-HS rats (p<0.05), but there was no difference in AT2-receptor expression in the renal medulla between CAP-HS, CAP-NS, and CON-HS rats. Likewise, there was no difference in AT1-receptor expression in mesenteric resistance arteries between CAP-HS, CAP-NS, and CON-HS rats. In contrast, mesenteric AT2-receptor expression was lower in CAP-HS than in CAP-NS and CON-HS rats (p<0.05). Tail-cuff systolic BP (mmHg) shows that blockade of the AT1-receptor with candesartan prevents the development of hypertension in CAP-HS rats (by the end of the experiment, CON-HS, 122±3; CAP-NS, 118±10; CAP-HS, 169±9; CAP-HS-CAN, 129±2, p<0.05). Thus, both circulating and tissue RAS in sensory-denervated rats are abnormally regulated in response to a high-salt intake, which may contribute to increased salt sensitivity and account for the effectiveness of candesartan in lowering BP in this model.

Endogenous angiotensin modulates PGE2-mediated release of substance P from renal mechanosensory nerve fibers

2002 ◽  
Vol 282 (1) ◽  
pp. R19-R30 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith
Keyword(s):  
Substance P ◽  
Nerve Fibers ◽  
Ang Ii ◽  
High Sodium ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Pelvic Perfusion ◽  
High Sodium Diet ◽  
Pelvic Pressure

Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA) by a prostaglandin E2(PGE2)-mediated release of substance P (SP) from renal pelvic sensory nerves. We examined whether the ARNA responses were modulated by high- and low-sodium diets. Increasing renal pelvic pressure resulted in greater ARNA responses in rats fed a high-sodium than in those fed a low-sodium diet. In rats fed a low-sodium diet, increasing renal pelvic pressure 2.5 and 7.5 mmHg increased ARNA 2 ± 1 and 13 ± 1% before and 12 ± 1 and 22 ± 2% during renal pelvic perfusion with 0.44 mM losartan. In rats fed a high-sodium diet, similar increases in renal pelvic pressure increased ARNA 10 ± 1 and 23 ± 3% before and 1 ± 1 and 11 ± 2% during pelvic perfusion with 15 nM ANG II. The PGE2-mediated release of SP from renal pelvic nerves in vitro was enhanced in rats fed a high-sodium diet and suppressed in rats fed a low-sodium diet. The PGE2 concentration required for SP release was 0.03, 0.14, and 3.5 μM in rats fed high-, normal-, and low-sodium diets. In rats fed a low-sodium diet, PGE2increased renal pelvic SP release from 5 ± 1 to 6 ± 1 pg/min without and from 12 ± 1 to 21 ± 2 pg/min with losartan in the incubation bath. Losartan had no effect on SP release in rats fed normal- and high-sodium diets. ANG II modulates the responsiveness of renal pelvic mechanosensory nerves by inhibiting PGE2-mediated SP release from renal pelvic nerve fibers.

Comparison of systemic and direct intrarenal angiotensin II blockade on sodium excretion in rats

1995 ◽  
Vol 269 (1) ◽  
pp. F40-F46 ◽  
Author(s):  
Y. Peng ◽  
F. G. Knox
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Sodium Excretion ◽  
Systemic Effects ◽  
Ang Ii ◽  
High Sodium ◽  
Sodium Diet ◽  
High Sodium Diet ◽  
Interstitial Infusion

To dissociate the renal effects from the systemic effects of angiotensin II blockade, the present study was designed to determine the effects of systemic and renal interstitial infusion of the specific angiotensin II (ANG II) receptor antagonist, losartan, on blood pressure and sodium excretion in rats fed a low-, normal, or high-sodium diet. Fractional sodium excretion (FENa) and mean arterial pressure (MAP) were measured in rats before and during systemic infusion of losartan (10 mg/kg) or renal interstitial infusion of losartan (3 mg/kg) by means of a chronically implanted matrix. In rats fed a low- or normal sodium diet, systemic infusion of losartan markedly decreased MAP (delta -21 +/- 2, delta -10 +/- 2 mmHg, respectively; P < 0.05) with an accompanying fall in FENa (delta -0.10 +/- 0.05, delta -0.91 +/- 0.40%, respectively; P < 0.05). In contrast, preferential blockade of renal ANG II with renal interstitial losartan infusion resulted in an increase in FENa (delta 0.13 +/- 0.04, delta 0.95 +/- 0.45%, respectively; P < 0.05) and no significant change in MAP. In rats fed a high-sodium diet, both systemic and renal interstitial infusion of losartan increased FENa (delta 1.90 +/- 0.26, delta 1.40 +/- 0.56%, respectively; P < 0.05). Although systemic infusion of losartan decreased MAP (delta -4.4 +/- 0.6 mmHg, P < 0.05) in rats fed a high-sodium diet, the reduction in MAP was much less than that in rats fed a low- and normal sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract P284: Angiotensin II Upregulates Cytochrome-450 4A Expression in Rat Kidney Through Type 1 Receptor

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Wanting Wang ◽  
Rong Rong ◽  
Osamu Ito ◽  
Yoshiko Ogawa ◽  
Yoshikazu Muroya ◽  
...  
Keyword(s):  
Renal Cortex ◽  
Urinary Albumin Excretion ◽  
Rat Kidney ◽  
At1 Receptor ◽  
Urinary Albumin ◽  
High Dose ◽  
At2 Receptor ◽  
Ang Ii ◽  
Outer Medulla

20-hydroxyeicosatetraenoic acids (20-HETE) is a cytochrome P-450 (CYP) 4A-dependent metabolite of arachidonic acid and regulates vascular tone and renal tubular function. Previous studies showed that angiotensin II (Ang II) stimulated the renal CYP activity and 20-HETE production through the Ang II type 1 (AT1) receptor and that the Ang II-increased the 20-HETE was linked to the Ang II type 2(AT2) receptor. Thus, the study was designed to clarify the role of Ang II in CYP4A isoforms expression in the rat kidney. Male Sprague-Dawley rats were infused Ang II at low dose (AL, 0.17mg/kg/min, sc) and high dose (AH, 0.70mg/kg/day, sc) by using osmotic mini pump, with or without AT1 receptor blocker candesartan (1 and 3mg/kg/day, po) for 1 week. The protein expression of CYP4A isoforms, AT1 receptor and AT2 receptor in the renal cortex, outer medulla, and inner medulla was examined by immunoblot analysis. The mRNA expression of CYP4A isoforms was examined by reverse transcription and polymerase chain reaction (RT-PCR). Ang II at high dose increased systolic blood pressure (control, 109±2; AH, 164±8 mmHg, p<0.01), creatinine (control, 0.24±0.00; AH, 0.29±0.01 mg/dl, p<0.01) and urinary albumin excretion (control, 20.3±5.9; AH, 2398.6±303.6 μg/mg creatinine, p<0.01). In the control group, the CYP4A1, 4A2, and 4A8 proteins were highly expressed in the renal cortex, lowly expressed in the outer medulla, barely detected in the inner medulla. The AT1 receptor was expressed in kidney sections; highly in the outer and inner medulla, the AT2 receptor was only detected in the outer medulla. Ang II dose-dependently increased all CYP4A isoform proteins in the renal cortex and outer medulla (CYP4A1, 24% and 222%; CYP4A2, by 51% and 258%; CYP4A8, by 52% and 550%, p<0.05). Ang II also increased all CYP4A isoform mRNAs in the renal cortex and outer medulla. The candesartan treatment dose-dependently inhibited the Ang II-increased blood pressure, creatinine, urinary albumin excretion and CYP4A isoform expressions. These results indicated that Ang II increases CYP4A isoform expressions in the kidney through AT1 receptor. The Ang II-upregulated CYP4A expressions may play an important role in hypertension and renal function.

scholarly journals Angiotensin AT2 receptor agonist prevents salt-sensitive hypertension in obese Zucker rats

2015 ◽  
Vol 308 (12) ◽  
pp. F1379-F1385 ◽  
Author(s):  
Quaisar Ali ◽  
Sanket Patel ◽  
Tahir Hussain
Keyword(s):  
Blood Pressure ◽  
Sodium Intake ◽  
Zucker Rats ◽  
Ang Ii ◽  
Maximal Increase ◽  
High Sodium ◽  
Sodium Diet ◽  
Angiotensin Type 2 Receptor ◽  
Obese Rats ◽  
Salt Sensitive Hypertension

High-sodium intake is a risk factor for the pathogenesis of hypertension, especially in obesity. The present study is designed to investigate whether angiotensin type 2 receptor (AT2R) activation with selective agonist C21 prevents high-sodium diet (HSD)-induced hypertension in obese animals. Male obese rats were treated with AT2R agonist C21 (1 mg·kg−1·day−1, oral) while maintained on either normal-sodium diet (NSD; 0.4%) or HSD (4%) for 2 wk. Radiotelemetric recording showed a time-dependent increase in systolic blood pressure in HSD-fed obese rats, being maximal increase (∼27 mmHg) at day 12 of the HSD regimen. C21 treatment completely prevented the increase in blood pressure of HSD-fed rats. Compared with NSD controls, HSD-fed obese rats had greater natriuresis/diuresis and urinary levels of nitrates, and these parameters were further increased by C21 treatment. Also, C21 treatment improved glomerular filtration rate in HSD-fed rats. HSD-fed rats expressed higher level of cortical ANG II, which was reduced to 50% by C21 treatment. HSD feeding and/or C21 treatment had no effects on cortical renin activity and the expression of angiotensin-converting enzyme (ACE) and chymase, which are ANG II-producing enzymes. However, ANG(1–7) concentration and ACE2 activity in the renal cortex were reduced by HSD feeding, and C21 treatment rescued both the parameters. Also, C21 treatment reduced the cortical expression of AT1R in HSD-fed rats, but had no effect of AT2R expression. We conclude that chronic treatment with the AT2R agonist C21 prevents salt-sensitive hypertension in obese rats, and a reduction in the renal ANG II/AT1R and enhanced ACE2/ANG(1–7) levels may play a potential role in this phenomenon.

Synergistic vascular effects of dietary sodium supplementation and angiotensin II administration

1997 ◽  
Vol 273 (3) ◽  
pp. H1275-H1282 ◽  
Author(s):  
B. Csiky ◽  
G. Simon
Keyword(s):  
Angiotensin Ii ◽  
Dietary Sodium ◽  
Ang Ii ◽  
Resistance Arteries ◽  
Vascular Effects ◽  
High Sodium ◽  
Sodium Diet ◽  
Term Administration ◽  
High Sodium Diet ◽  
Sodium Supplementation

The hypertensinogenic action of dietary sodium supplementation was investigated in angiotensin II (ANG II)-treated rats. We hypothesized that high-sodium diet would potentiate ANG II-induced vasoconstriction and hypertension, including the development of structural vascular changes, through synergistic action with ANG II in stimulating sympathetic activity and vascular growth. Mesenteric vasoconstrictor responses to ANG II, norepinephrine (NE), arginine vasopressin (AVP), and periarterial nerve stimulation were measured in Sprague-Dawley rats after 7-10 days of the following treatments: 200 ng.kg-1.min-1 ip ANG II (n = 12), 4% NaCl diet (n = 11), ANG II + 4% NaCl diet (n = 7), and 0.7% NaCl diet (controls) (n = 15). Additional rats received 50 ng.kg-1.min-1 sc ANG II (n = 8), 2% NaCl diet (n = 9), ANG II + 2% NaCl diet (n = 6), or 0.7% NaCl diet (controls) (n = 10) for 12 wk. Systolic blood pressure (SBP) values were measured weekly for 4 wk and then every other week for 8 wk. Then, the wall-to-lumen ratio (W/L) of mesenteric resistance arteries (< 150 microns OD) was measured after in situ perfusion-fixation. After 7-10 days of treatment, there were no significant changes in SBP in any of the groups. High-sodium diet increased vasoconstrictor responses to ANG II (P < 0.01) and nerve stimulation (P < 0.02), but not to NE or AVP, and in combination with ANG II treatment further potentiated vasoconstrictor responses to ANG II (synergism). After 12 wk of treatment, ANG II increased W/L of small resistance arteries by 11% (P < 0.05) without a significant rise in SBP. ANG II and 2% NaCl diet in combination raised SBP by 36 mmHg (P < 0.01) and increased small artery W/L by 28% (P < 0.001) compared with values obtained in control rats. To test the specificity of the interaction between ANG II and high-sodium diet, all the experiments were repeated during phenylephrine (PE, 10 micrograms.kg-1.min-1 sc) treatment of rats. PE by itself or in combination with high-sodium diet had no effect on the measured parameters. Thus short-term administration of high-sodium diet appears to potentiate vasoconstrictor responses to ANG II by facilitating sympathetic neurotransmission, and long-term administration of high-sodium diet raises SBP by potentiating the trophic vascular effects of ANG II. The interaction appears to be specific to ANG II and is occurring on the vascular level.

scholarly journals Sex differences in acute ANG II-mediated hemodynamic responses in mice

2010 ◽  
Vol 299 (3) ◽  
pp. R899-R906 ◽  
Author(s):  
Markus P. Schneider ◽  
Paul F. Wach ◽  
Melissa K. Durley ◽  
Jennifer S. Pollock ◽  
David M. Pollock
Keyword(s):  
Sex Differences ◽  
Receptor Expression ◽  
At2 Receptor ◽  
Ang Ii ◽  
High Sodium ◽  
Low Sodium ◽  
Oxide Synthase ◽  
Renal Vascular ◽  
Endothelial Nitric Oxide

Male sex is associated with higher blood pressure and greater renal injury, perhaps related to greater sensitivity to ANG II. In anesthetized male and female C57BLK/6 mice, we assessed responses of mean arterial pressure (MAP) and renal vascular resistance (RVR; Transonic flow probe) to acute bolus injections of ANG II (0.3–3.0 μg/kg iv) and phenylephrine (PE; 30–300 μg/kg) during low-, normal-, and high-sodium diets. The role of reactive oxygen species was determined by coadministration of tempol. ANG II type 1 and type 2 (AT1 and AT2) receptor and endothelial nitric oxide synthase (NOS3) expression were determined in dissected kidney vessels. While no difference was found on the low-sodium (LS) diet, MAP and RVR responses to ANG II were greater in males during the normal-sodium (NS) and high-sodium (HS) diets (e.g., RVR response at ANG II 3.0 μg/kg during NS: +329 ± 22 vs. +271 ± 28 mmHg·ml−1·min, P = 0.029, effect size = 0.75). Tempol had no effect on the sex-dependent responses on any of the diets. On the LS diet, AT1 and AT2 receptor expression was higher in males. No sex differences were found on the NS diet. On the HS diet, AT1 was higher, and NOS3 expression was lower in males. Acute responses to ANG II are greater in male mice during NS and HS diets, which is, in part, related to differences in AT1, AT2, and NOS3 expression in kidney vessels. Mouse models will be useful to study the role of sex differences in ANG II sensitivity for cardiovascular and renal disease.

Plasma Angiotensin II Concentration Regulates Vascular but Not Adrenal Responsiveness to Restriction of Sodium Intake in Normal Man

1981 ◽  
Vol 61 (5) ◽  
pp. 527-534 ◽  
Author(s):  
Bess F. Dawson-Hughes ◽  
T. J. Moore ◽  
R. G. Dluhy ◽  
N. K. Hollenberg ◽  
G. H. Williams
Keyword(s):  
Sodium Intake ◽  
Regression Line ◽  
Sodium Balance ◽  
Ang Ii ◽  
High Sodium ◽  
Sodium Diet ◽  
High Sodium Intake ◽  
Low Sodium ◽  
Vascular Responsiveness ◽  
High Sodium Diet

1. Sodium restriction increases adrenal and decreases vascular sensitivity to angiotensin II (ANG II). These responses may be mediated either by the circulating level of ANG II or other mechanisms also modified by a change in sodium balance. To assess the importance of the ANG II level, captopril, an oral converting enzyme inhibitor, was used to lower the plasma ANG II level to the sodium-loaded range while maintaining subjects in low sodium balance. 2. Normal volunteer subjects received an infusion of ANG II in increasing doses in three states: high sodium intake, low sodium intake and low sodium intake after pretreatment with captopril. 3. Basal levels of ANG II on high-sodium diet and low-sodium diet plus captopril were similar. In the ANG II infusion studies the slope of the aldosterone—ANG II regression line on low sodium intake was significantly steeper than that on high sodium intake. After the addition of captopril the slope was not decreased, indicating that the endogenous ANG II concentration is not necessary to maintain adrenal sensitivity during sodium restriction. 4. In the ANG II infusion studies the slope of the mean blood pressure—ANG II regression line on high sodium intake was significantly steeper than that on low sodium intake. The addition of captopril to sodium-restricted subjects caused the slope of the regression relationship to increase significantly, consistent with an enhanced vascular responsiveness when endogenous ANG II levels were lowered. However, the slope on low sodium plus captopril did not increase to the level of subjects on a high-sodium diet, suggesting that factors in addition to the circulating ANG II level are also important in regulating the vascular responsiveness to ANG II.

scholarly journals Role of renin-angiotensin-aldosterone system in salt-sensitive hypertension induced by sensory denervation

2001 ◽  
Vol 281 (5) ◽  
pp. H2143-H2149 ◽  
Author(s):  
Yan Huang ◽  
Donna H. Wang
Keyword(s):  
Blood Pressure ◽  
Plasma Renin ◽  
Male Rats ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
High Sodium ◽  
Sodium Diet ◽  
Sensory Denervation ◽  
Salt Sensitive Hypertension

To define the role of the renin-angiotensin-aldosterone system in a novel salt-sensitive model, neonatal Wistar rats were given capsaicin (50 mg/kg sc) on the first and second days of life. After weaning, male rats were divided into the following six groups and treated for 3 wk with: control + normal sodium diet (CON-NS), CON + high-sodium diet (CON-HS), CON + HS + spironolactone (50 mg · kg−1 · day−1, CON-HS-SP), capsaicin pretreatment + NS (CAP-NS), CAP-HS, and CAP-HS-SP. Radioimmunoassay shows that plasma renin activity (PRA) and plasma aldosterone level (PAL) were suppressed by HS, but they were higher in CAP-HS than in CON-HS and CON-HS-SP ( P < 0.05). Both tail-cuff systolic blood pressure and mean arterial pressure were higher in CAP-HS than in all other groups ( P < 0.05). Urine water and sodium excretion were increased with HS intake, but they were lower in CAP-HS than in CON-HS ( P < 0.05). Western blot did not detect differences in adrenal AT1 receptor content. Therefore, insufficiently suppressed PRA and PAL in response to HS intake by sensory denervation may contribute to increased salt sensitivity and account for effectiveness of spironolactone in lowering blood pressure in this model.

Differential effects of endothelin on activation of renal mechanosensory nerves: stimulatory in high-sodium diet and inhibitory in low-sodium diet

2006 ◽  
Vol 291 (5) ◽  
pp. R1545-R1556 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith
Keyword(s):  
Substance P ◽  
Dietary Intake ◽  
Sensory Nerves ◽  
High Sodium ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Salt Sensitive Hypertension ◽  
High Sodium Diet ◽  
Pelvic Pressure

Activation of renal mechanosensory nerves is enhanced by high and suppressed by low sodium dietary intake. Afferent renal denervation results in salt-sensitive hypertension, suggesting that activation of the afferent renal nerves contributes to water and sodium balance. Another model of salt-sensitive hypertension is the endothelin B receptor (ETBR)-deficient rat. ET and its receptors are present in sensory nerves. Therefore, we examined whether ET receptor blockade altered the responsiveness of the renal sensory nerves. In anesthetized rats fed high-sodium diet, renal pelvic administration of the ETBR antagonist BQ-788 reduced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mmHg from 26 ± 3 to 9 ± 3% and the PGE2-mediated renal pelvic release of substance P from 9 ± 1 to 3 ± 1 pg/min. Conversely, in rats fed low-sodium diet, renal pelvic administration of the ETAR antagonist BQ-123 enhanced the ARNA response to increased renal pelvic pressure from 9 ± 2 to 23 ± 6% and the PGE2-mediated renal pelvic release of substance P from 0 ± 0 to 6 ± 1 pg/min. Adding the ETAR antagonist to ETBR-blocked renal pelvises restored the responsiveness of renal sensory nerves in rats fed a high-sodium diet. Adding the ETBR antagonist to ETAR-blocked pelvises suppressed the responsiveness of the renal sensory nerves in rats fed a low-sodium diet. In conclusion, activation of ETBR and ETAR contributes to the enhanced and suppressed responsiveness of renal sensory nerves in conditions of high- and low-sodium dietary intake, respectively. Impaired renorenal reflexes may contribute to the salt-sensitive hypertension in the ETBR-deficient rat.

Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves

2006 ◽  
Vol 291 (6) ◽  
pp. H3136-H3143 ◽  
Author(s):  
Youping Wang ◽  
Alex F. Chen ◽  
Donna H. Wang
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Protein Expression ◽  
Creatinine Clearance ◽  
Renal Cortex ◽  
Sensory Nerves ◽  
Male Rats ◽  
Sod Activity ◽  
Sodium Diet ◽  
Salt Sensitive Hypertension

To determine the mechanism(s) underlying enhanced oxidative stress in kidneys of salt-sensitive hypertension, neonatal Wistar rats were given vehicle or capsaicin (CAP, 50 mg/kg sc) on the first and second days of life. After being weaned, male rats were assigned into four groups and treated for 2 wk with the following: vehicle + a normal sodium diet (NS, 0.4%, CON-NS), vehicle + a high-sodium diet (HS, 4%, CON-HS), CAP + NS (CAP-NS), and CAP + HS (CAP-HS). Systolic blood pressure was significantly increased in CAP-HS but not CAP-NS or CON-HS rats. Plasma and urinary 8-iso-prostaglandin F2α levels increased by ∼40% in CON-HS and CAP-HS rats compared with their respective controls fed a NS diet ( P < 0.05), and these parameters were higher in CAP-HS compared with CON-HS rats. Superoxide (O2−·) levels in the renal cortex and medulla increased by ∼45% in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats ( P < 0.05). Enhanced O2−· levels in the cortex and medulla in CAP-HS rats were prevented by preincubation of renal tissues with apocynin, a selective NAD(P)H oxidase inhibitor. Protein expression of NAD(P)H oxidase subunits, including p47phox and gp91phox in the renal cortex and medulla, was significantly increased in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats. In contrast, protein expression and activities of Cu/Zn SOD and Mn SOD were significantly increased in the renal medulla in both CAP-HS and CON-HS but in the cortex in CAP-HS rats only. Creatinine clearance decreased by ∼45% in CAP-HS rats compared with CON-HS, CON-NS, and CAP-NS rats ( P < 0.05). O2−· levels in the renal cortex of CAP-HS rats negatively correlated with creatinine clearance ( r = −0.76; P < 0.001). Therefore, regardless of enhanced SOD activity to suppress oxidative stress, increased oxidative stress in the kidney of CAP-treated rats fed a HS diet is likely the result of increased expression and activities of NAD(P)H oxidase, which may contribute to decreased renal function and increased blood pressure in these rats. Our results suggest that sensory nerves may play a compensatory role in attenuating renal oxidative stress during HS intake.

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