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The role of the kidney in the control of blood pressure has been convincingly demonstrated by several studies. Recent evidence has suggested that subtle acquired tubulointerstitial injury may cause a defect in sodium excretion function, thus leading to salt-sensitive hypertension. There are no reports, however, examining the effect of experimental chronic pyelonephritis on renal sodium handling and arterial pressure. Thus, to examine the influence of salt intake and unilateral nephrectomy, unanesthetized, unrestrained rats were randomly assigned to one of two separate groups: sham-operated rats (CO) or chronic unilateral pyelonephritic rats (CP). After twenty one days, the pyelonephritic group was subdivided in two: one subgroup continued with water intake (CPw), while the other was changed to 0.9% NaCl intake (CPs), like the control group (COs). After seven days, all rats were submitted to unilateral nephrectomy of the left normal kidney. Data presented herein show that chronic pyelonephritis produced an increase in mean arterial pressure (CO: 121.4 +/- 1.0 mmHg to CP: 127.0 +/- 0.9 mmHg, p = 0.000) that was enhanced by saline ingestion (COs: 121.6 +/- 1.4 mmHg; CPw: 127.0 +/- 1.8 mmHg; CPs: 132.1 +/- 1.2 mmHg, p = 0.000) and further aggravated by unilateral nephrectomy (CO: 125.2 +/- 2.6 mmHg; CPw: 127.5 +/- 0.9 mmHg; CPs: 139.2 +/- 1.1 mmHg, p = 0.000). Unchanged blood pressure measurements (120.2 +/- 2.3 mmHg) were observed beyond 21 days in control rats maintained on water regimen when compared with saline-drinking groups. These changes in mean arterial pressure were observed despite an increased fractional sodium excretion in the CPs group compared to the other groups before uninephrectomy (COs: 0.125 +/- 0.025%; CPw: 0.045 +/- 0.013%; CPs: 0.292 +/- 0.046%; p = 0.000), as compared to CPw after uninephrectomy (COs: 0.249 +/- 0.077%; CPw: 0.062 +/- 0.011%; CPs: 0.363 +/- 0.195%, p = 0.019). In addition, it was shown that daily liquid intake was higher in CPs than in CPw but similar to COs, both before uninephrectomy (COs: 42.8 +/- 2.6 ml/d; CPw: 34.3 +/- 3.5 ml/d; CPs: 51.8 +/- 3.7 ml/d, p = 0.006) and after uninephrectomy (COs: 40.9 +/- 5.5 ml/d; CPw: 33.8 +/- 1.4 ml/d; CPs: 53.0 +/- 3.5 ml/d, p = 0.004). The current data suggest that chronic pyelonephritis promotes an inability of renal tubules to handle sodium excretion when exposed to sodium overload and aggravated by uninephrectomy, thus constituting a model for salt-sensitive hypertension.

Bartter's syndrome is a disorder that has been linked to mutations in one of three ion transporter proteins: NKCC2 (type I), ROMK (type II) and CCLNKB (type III), which affects a final common pathway that participates in ion transport by thick ascending limb cells. We present an atypical case of mitochondriopathy combined with tubule functional disturbances compatible with Bartter's syndrome and definitive sensorineural blindness. Our patient had a peculiar clinical presentation with signs of salt and volume depletion, low blood pressure and secondary hyperaldosteronism, associated with hypokalemic metabolic alkalosis, hypocalcemia and severe hypomagnesemia, uncommon in genetic forms of Bartter's syndrome. The enhanced absolute and fractional sodium excretion in our patient compared to volunteers was accompanied by increased post-proximal sodium rejection, suggesting a striking ion transport dysfunction in these nephron segments. These findings lead to the Bartter's syndrome diagnosis, accompanied by a suppose mitochondrial tick ascending loop of Henle epithelium dysfunction that may reflect the high energy supplied by mitochondria electron transport chain, required for this nephron segment to maintain normal ion transport.

Much effort has been made in recent years to clarify metabolic and renal function changes in sepsis. A number of studies performed in different models of sepsis have been described. One such model that is frequently used is cecal ligation and puncture (CLP) in rats. This model resembles human sepsis in several important aspects, such as an early phase of hyperdynamic, hypermetabolic sepsis followed by a late hypodynamic, hypometabolic phase. The present study evaluated the blood pressure (n = 5) and renal function changes during development of CLP renal failure and to determine the effects of NOS inhibition (L-NAME) and 0.15 M NaCl administration on tail blood pressure and renal function in randomly assigned five groups (n = 10 each): (1) Sham-operated, (2) Sham-operated L-NAME-treated, (3) CLP rats, (4) CLP L-NAME-treated, and (5) CLP 0.15 M NaCl-treated rats. The basal tail blood pressure was not significantly different among the four groups. One week later, arterial pressure was significantly increased in sham-operated L-NAME-treated rats (159 +/- 12 mmHg) compare with the other groups (118 +/- 9.0 mmHg in nontreated rats, p < 0.05). Blood pressure shows a slightly and not significant decrease up to 12h in L-NAME and 0.15 M NaCl treated rats, which in turn was followed by a significant reduced arterial pressure 18h after CLP in both groups (L-NAME: 96.0 +/- 3.6 mmHg, p < 0.05) and NaCl: 82.3 +/- 2.4 mmHg, p < 0.05) compared to sham-operated groups. The glomerular filtration rate estimated by CCr decreases significantly in the CLP untreated group (p < 0.001) and did not significantly differ from the sham-operated and L-NAME-treated groups (p = 0.4) during the studies of renal tubule sodium handling. On the other hand, subcutaneous 0.15 M NaCl administration prevented CCr decreases in CLP rats (p = 0.25). CLP increased the FENa in the sham-operated from: 857.2 +/- 85.1 delta%min(-1) to CLP: 1197.8 +/- 119.0 delta%min(-1). The high FENa to CLP was blunted and significantly reduced by previous systemic treatment of animals with L-NAME from sham-operated+L-NAME: 1368.0 +/- 72.0 delta%min(-1) to CLP+L-NAME: 1148.0 +/- 60.4 delta%min(-1) (p < 0.01). The enhanced FENa in the CLP group were accompanied by a significant increase in proximal sodium reabsorption rejection. The salient findings of the present study suggest that a decrease in the blood pressure and creatinine clearance caused by CLP may benefit from L-NAM and fluid resuscitation during initial bacteremia (first 12 h) by promoting an additional increase of tubule sodium reabsorption in the post-proximal segments of nephrons, but these therapies could not prevent acute renal failure after established endotoxemia.

Sodium retention is a frequent effect of cancer in humans and animals, but the mechanism involved is not yet understood. In the Walker-256 tumor, sodium retention has been considered to be a late effect, secondary to retention in the tumor mass, and/or to adrenal hypertrophy. Normally, (in rats receiving single tumor implants), the development of different tumor systemic effects (TSE) such as anorexia, sodium and fluid retention, anemia and immune depression in rats is synchronous within each individual but random among individuals of a given group in which they appear 6-47 days, or more, after inoculation. In present study, multifocal simultaneous inoculations of tumor cells resulted in a rapid and synchronous initiation of TSE (in 3-4 days) in all rats when no local effects of metastases could mask the results. Sodium retention is a special tumor effect on Na+ balance and a very sensitive indicator of TSE initiation. The results from multifocally inoculated rats were averaged in each (sub-clinical (SubC), moderate (mCP) and grave (gCP)) clinical phase and compared to food-restricted (FR) rats. There was a significant, early decrease in urinary Na+ excretion during mCP when compared to SubC and FR. The renal sites involved were studied in awake, unrestrained animals by measuring of sodium, creatinine and lithium clearances. There was an initial increase in the absolute proximal (mCP: 21.4 +/- 1.7 vs FR: 16.0 +/- 1.1 mmol/min/100 g b.w., p < 0.05) and post-proximal (mCP: 11.1 +/- 0.4 vs FR: 6.6 +/- 0.4 mmol/min/100 g b.w., p < 0.001) Na+ reabsorption, which were partially compensated for by a rise in glomerular filtration rate (mCP: 213 +/- 11.4 vs FR: 162 +/- 10.2 microL/min/100 g b.w., p < 0.01) and by a fall in fractional proximal Na+ reabsorption (mCP: 62.8 +/- 2.2% vs FR: 70.1 +/- 1.7%, p < 0.05), despite significant Na+ and fluid retention. The terminal phase of illness (gCP) culminated with a marked decrease in creatinine clearance, suggesting a significant fall in renal function. The multifocal model proved useful for studying the initial TSE, since the sites of action would, in principle, be easy to identify. These observations may be of physiological interest since TSE may result from the abnormal production of physiological modulators.

Paucity studies have indicated that a systemic metabolic acidosis cause a decrease in salt and water reabsorption in the kidney. The following study was undertaken on male Wistar-Hannover rats (200-250 g) to investigate the effects of a chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in sham-operated and uninephrectomized rats, by lithium clearance. The present study shows that chronic acidosis (blood pH, 7.16 +/- 0.13) caused a sustained increase in renal fractional Na+ excretion (267.9 +/- 36.4%), accompanied by a rise in the fractional proximal (113.3 +/- 3.6%) and post-proximal (179.7 +/- 20.2%) Na+ and fractional K+ (163.4 +/- 5.6%) excretions when compared to pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. On the other hand, a body growth impairment was observed in the acidotic (control, 258 +/- 3.7 g versus acidotic, 232 +/- 4.6 g) and pair-fed rats (225 +/- 3.6 g), whereas there was significant enhance in the kidney weights in acidotic rats (1.73 +/- 0.05 g) compared to other experimental groups (control, 1.46 +/- 0.05 g; pair-fed, 1.4 +/- 0.05 g). The renal growth indexes after metabolic acidosis NH4Cl-induced did not shown statistical difference at 1.5, 3.0 and 12 hours after uninephrectomy when were compared with pair-fed groups. However, from the fifth to tenth day after unilateral nephrectomy the renal growth index of acidotic group was significantly greater than pair-fed groups. Unilateral nephrectomy in acidotic animals caused a striking additional but transient increase in fractional renal sodium (FENa+) and potassium (FEK+) excretion from 1.5 to 3 hours post-surgery meanly associated with an enhanced post-proximal sodium excretion when compared to pair-fed uninephrectomized rats. By the fifth postoperative day the all functional values returned to baseline levels. This altered renal Na+ handling and K+ excretion may result from a reciprocal relationship between tubular metabolic pathway stimuli and ion transport. Further studies are required to investigate the acidosis involvement on functional kidney response.

We studied the actions of nifedipine and the platelet activating factor (PAF) antagonist BN 52021 on renal and tubular function in glycerol-induced acute renal failure (Gly-ARF). The tubular handling of sodium was evaluated through the lithium clearance method in awake rats in metabolic cages. The sequential analysis of tubular function 3, 6, 12, and 24 h after Gly-ARF showed a sharp decrease in fractional proximal Na reabsorption (FPRNa)--control 74.1 +/- 12.5%, 3 h: 79.5 +/- 6.0%; 6 h: 41.8 +/- 15.9%; 12 h: 22.9 +/- 17.9%; and 24 h: 31.1 +/- 16.2% (p < 0.001) while fractional distal Na reabsorption (FDRNa) did not change during the study. The effect of nifedipine (20 mg/kg p.o.) and BN 52021 (1 mg/kg i.p.) were evaluated 24 h after the induction of Gly-ARF. Both drugs attenuated the reduction in creatinine clearance (control 431.8 +/- 108.2, glycerol 96.7 +/- 43.8, glycerol plus nifedipine 264.9 +/- 103.5, and glycerol plus BN 52021 188.9 +/- 69.8 microL/min/100 g, p < 0.001). However, only nifedipine could keep FPRNa higher than untreated rats (58.3 +/- 13.2 vs. 31.1 +/- 16.2%, p < 0.05) and reduced the tubular necrosis on histologic semiquantitative analysis. Our data showed that nifedipine and BN 52021 could protect against filtration failure in Gly-ARF but that only nifedipine reduced the proximal tubular lesion.