Search

The early renal response to unilateral ureteral occlusion (UUO) and its mechanism have been extensively studied in dogs but seldom discussed in the most frequently used laboratory animals, rats. The acute phase of the renal response to UUO was studied in female rats weighing 190-236 g. We recorded the ureteral pressure and changes in renal parameters throughout 120 minutes of UUO in control (US, UUO + saline, n = 10), L-arginine-treated (UA, n = 10), and right-nephrectomized rats (UO, UUO in one kidney, n = 9). Ureteral pressure increased in all three groups of rats after complete ureteral obstruction. The extent of the increase was not significantly different between US and UA rats but was significantly higher in the UO rats. In US rats, the cortical microvascular blood flow (CMVBF), measured by a laser Doppler flowmeter, declined significantly, from 321 +/- 10 perfusion units (PU) to 260 +/- 11 PU. The percentage of drop in CMVBF at 120 minutes of UUO was significantly greater in UO (25.7 +/- 3.8 %) than in US (19 +/- 2.1%) and in UA (14 +/- 2%) rats. Acute UUO reduced the glomerular filtration rate (GFR) in US and UO rats, whereas L-arginine attenuated this decrease. The excretion of nitrate/nitrite was increased after UUO. Giving N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 12 mg/kg/h) during UUO did not reduce CMVBF more severely. Western blot analysis of endothelial nitric oxide synthase expression in the renal cortex and medulla protein extracts revealed no differences between US and sham-operated rats. Acute UUO did not lead to renal hyperemia in rats. Reduction of nitric oxide during UUO might contribute to the decrease of renal circulation during UUO.

The sympathetic nervous system is activated in response to altitude hypoxia and activation of renal sympathetic nerves may cause vasoconstriction and fluid retention. However, renal excretion does not differ significantly between rats exposed to high altitude hypoxia and control rats. We hypothesize that renal response to norepinephrine (NE) is altered after chronic hypoxia. Female Wistar rats weighing 200 to 220 g were exposed to hypoxia in an altitude chamber (5,500 m, 380 torr) 15 hours/day for 4 weeks (HA, high altitude). Our findings showed that systemic infusion of NE (300 micrograms.kg-1.hr-1) produced less diuresis/natriuresis in HA rats that in sea level (SL) controls. With mechanical elevation of arterial blood pressure, both SL and HA rats showed no significant difference in their response to pressure diuresis. Direct intrarenal arterial NE (10 micrograms.kg-1.hr-1) administration reduced renal function more in HA rats than in SL rats. Intrarenal arterial administration of L-arginine (100 micrograms.kg-1.hr-1) did not alter the renal action of NE in HA rats. However, with intrarenal arterial infusion of phosphoramidon (100 micrograms.kg-1.hr-1), NE increased renal response in HA rats to almost the same level as that in SL rats. These results suggest that HA rats may have either an excess renal action of antidiuretic and antinatriuretic factors or an insufficient renal action of diuretic and natriuretic factors during NE administration.

Multifiber renal afferent nerve activity responds to volume expansion in sea level rats but not in chronically hypoxic (high altitude) rats. We performed single-unit recordings of renal afferent nerve activity to characterize renal sensory receptors and their responses to volume expansion in these animals. Hypoxia was induced by placing Wistar rats in an altitude chamber (380 Torr, 5,500 m) for 4 wk. Spontaneously firing renal R2 chemoreceptor and arterial, ureteropelvic, and venous mechanoreceptors were identified. The basal activity of each receptor was similar among these rats. In response to specific stimulus, the increasing impulse of R2 chemoreceptor was similar between two groups of rats, but the increasing activity of each mechanoreceptor was less in hypoxic rats. When challenged with saline load, R2 chemoreceptor activity decreased, but all mechanoreceptors activated in all rats. Despite similar increases of arterial, renal ureteropelvic, and venous pressure during saline load, the increasing activity of each mechanoreceptor was significantly less in hypoxic rats. These results indicated chronic hypoxia attenuates the sensitivity of renal mechanoreceptors in response to the stimulation of saline load.

Background: We studied the renal action of substance P (SP) in rats chronically exposed to hypoxia (high altitude, HA), compared to control rats kept at sea level (SL)., Methods: Hypoxia was induced by placing female Wistar rats (182-225 g) in an altitude chamber (5500 m) 15 h.d-1 for 4 weeks., Results: Intrarenal arterial infusion of substance P (60 ng.kg-1. h-1) increased the excretion of urine, sodium in both groups of rats, however, the excretion of kallikrein (KK) and the glomerular filtration rate (GFR) were not significantly altered. After aprotinin (10,000 kiu.kg-1. min-1) treatment, kallikrein was depleted, and substance P lost its diuretic action. Spantide, an SP antagonist (6000 ng.kg-1. h-1, I.V.) decreased urine, and urinary excretion of sodium and potassium in SL rats, but not in HA rats. Acute renal denervated diuresis in SL rats was not modified after Spantide administration. Finally, it was found that both SP and SP antagonist did not significantly change the renal parameters in either group of rats after chronic renal denervation., Conclusion: We made the following conclusions: a) endogenous renal action of SP was suggested in SL but not in HA rats; b) the renal action of SP might be through KK release, although urinary KK did not increase after SP administration; and c) SP action is renal nerve dependent in both groups of rats.

1. We have studied the role of kallikrein (KK) in the maintenance of renal function in chronic hypoxic rats (high altitude; HA), compared with control rats kept at sea level (SL). Hypoxia was induced by placing female Wistar rats (198-290 g) in an altitude chamber (5500 m) 15 h/day for 4 weeks. Experiments were also conducted to study the interaction of KK with renal nerve activity and endothelin (ET), two parameters previously shown to be altered in this model. 2. It was found that renal cortex tissue KK activity (TKA) was not significantly different in 10 SL and 10 HA rats. However, the urinary KK activity (UKA) was reduced nearly to half (from 35.2 +/- 4.6 to 18.5 +/- 1.7 pkat/min) in HA rats after 4 weeks of chronic hypoxia. 3. Acute renal denervated diuresis was accompanied by a significant increase in UKA (from 9 +/- 2 to 14 +/- 2 pkat/min in HA and denervated HA rats, respectively; P < 0.05) in HA rats. Intrarenal arterial pretreatment of aprotinin reduced the denervated diuresis. 4. Endothelin (600 ng/kg per h) reduced urine flow, sodium and potassium excretion in the ipsilateral kidney in another 10 SL and 10 HA rats. The extent of the drop of these parameters was significantly less in HA rats. Urinary KK activity was correlated significantly with the measured renal functional parameters (r ranging from 0.472 to 0.612) in SL rats, but was insignificant in HA rats (r ranging from 0.032 to 0.192). 5. We have demonstrated that chronic exposure to hypoxia decreases urinary KK excretion and that KK is involved in acute renal denervated diuresis generated in these animals. The present study suggests that KK plays a partial role in the maintenance of renal function in chronic hypoxic rats.

Four renal cell lines were derived from glomeruli, proximal, distal, and cortical collecting tubules microdissected from the kidneys of transgenic mice carrying the temperature-sensitive mutant of the simian virus 40 large T antigen under the control of the vimentin promoter. All four cell lines contained large T antigen in their nuclei, grew rapidly, and contained vimentin filaments when grown in serum-enriched medium at the permissive temperature of 33 degrees C. The glomerular cell line formed multiple layers of cells and contained smooth muscle actin and desmin filaments, features of mesangial cells. The three tubule cell lines formed monolayers of polarized cuboid cells separated by tight junctions and having a patchy distribution of cytokeratins K8-K18. A shift from 33 degrees C to the restrictive temperature (39.5 degrees C) stopped cell growth in all cell lines and caused profound changes in the content of intermediate filaments. Vimentin was still present in mesangial-like cells, but the proximal, distal, and collecting tubule cells contained uniform networks of cytokeratins K8-K18 and desmoplakin I and II around the cell peripheries. Potassium transport, mediated by Na+-K+ ATPase pumps and specific cAMP hormonal sensitivities, significantly increased in proximal, distal, and collecting tubule cells when shifted from 33 degrees C to 39.5 degrees C. Thus, the temperature-dependent inactivation of large T antigen, responsible for the arrest of cell growth, did not affect the phenotype of mesangial-like glomerular cells but induced some changes in the expression of intermediate filaments and restored, at least partially, the main parental cell-specific functions in proximal, distal, and collecting tubule cultured cells.

This work was designed to study the significance of the renal nerves in chronic hypoxic (high-altitude; HA) rats after saline loading. Female Wistar rats (200-290 g) under sodium pentobarbital (40 mg/kg i.p.) anesthesia were used in these experiments. Hypoxia was induced by placing the rats in an altitude chamber (5,500 m) for 4 weeks. Both the renal efferent nervous activity (RENA) and the renal afferent nervous activity (RANA) were recorded simultaneously throughout the experimental period. It was found that the responses of RENA and RANA to an intravenous saline infusion (10 ml, 10 min) were significantly different between the sea level (SL) control and HA rats. In SL rats, a depression of RENA was found; the depressed RENA had not recovered 80 min after cessation of the saline infusion. In HA rats, an initially depressed RENA was also found; however, it returned to the control level within 10 min following the cessation of saline infusion. RANA enhanced twice a few minutes after saline loading in SL rats; however, the changes of RANA in HA rats were not significant. In both groups of rats, whether renally denervated or intact, the amount of excretory urine and sodium after saline loading was unchanged. The renal norepinephrine levels were also measured by a high-pressure liquid chromatography system in both groups of rats, and it was found that the renal norepinephrine content of the HA rats was significantly higher than in the SL rats.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to investigate the possible role of renal nerves in the regulation of renal function after the application of heat (BH), by means of an electric heating pad (42 +/- 1 degree C) to the skin of the back overlying the kidneys. Both renal efferent (RENA) and renal afferent nervous activity (RANA) were recorded in 7 anesthetized female Wistar rats. It was found that RENA reduced to less than 80% of the control level during 30 min of back heating, accompanied by an increase in excretion of urine, sodium and potassium, and enhanced the glomerular filtration rate. BH in 9 chronic bilateral renal denervated rats (RD) showed the same renal responses as in the renal nerve intact rats (RI) after back heating. It is concluded that renal nerves played only a partially role in the renal diuretic action of back heating.

1. The direct renal effects of endothelin (ET) were studied in eight chronic hypoxic rats (HA) and eight sea level (SL) spontaneously hypertensive rats (SHR). 2. After 4 weeks of exposure to simulated 5486 m (18,000 ft) hypoxia, all HA rats were in apparently good health, and baseline renal function, except effective renal blood flow, was not significantly different from SL rats. 3. Intrarenal arterial administration of ET (600 ng/kg per h) reduced ipsilateral renal excretion of water, sodium and potassium, glomerular filtration rate and effective renal plasma flow in both SL and HA rats to almost the same extent. 4. Administration of ET antiserum, however, increased the renal excretion of water in HA rats. 5. It is concluded that ET may play a role in the renal regulation of chronic hypoxic SHR.