摘要:

The recent development of a transgenic rat strain bearing the mouse ren-2 renin gene [TGR(mRen2)27] has provided a new monogenetic model of hypertension. Other hypertensive rat strains are characterized by a blunted pressure-diuresis-natriuresis response such that higher renal perfusion pressures are required to excrete normal amounts of water and sodium. Dysfunction of the renin-angiotensin and nitric oxide systems may cause in this abnormality. This study examined the effect of enalapril on the pressure-natriuresis response and urinary nitric oxide metabolite excretion in 6-month-old TGR(mRen2)27 rats. The slope of the line relating renal perfusion pressure and urine flow rate in TGR (0.08 ± 0.01 µl · min-1 · g kidney weight-1 · mm Hg-1) was significantly lower than that in control rats (0.15+0.01 µl·min-1 g kidney weight-1 mm Hg-1). Pressure-natriuresis responses were also shifted to higher pressure levels in TGR. Treatment with enalapril for 3 months lowered the mean arterial pressure from 94 ± 2 to 84 ± 4 mm Hg in control rats and from 146 ± 3 to 89+3 mm Hg in TGR. The slopes of lines relating renal perfusion pressure and urine flow rate as well as sodium excretion were significantly increased by enalapril in control and transgenic animals. Urinary nitric oxide metabolite excretion rose similarly with increasing renal perfusion pressure in both control and TGR rats and was not affected by enalapril. These results confirm that older TGR rats have a blunted pressure -diuresis-natriuresis response that can be corrected by inhibition of the renin-angiotensin system and suggest that their production of nitric oxide

ISSN:1420-4096    

DOI:10.1159/000174116

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The renal endothelin (ET) system has been claimed to play an important role in the regulation of renal blood flow (RBF) and sodium excretion in primary hypertension. The aim of the present study was to investigate the contribution of the endogenous ET system in the autoregulation of total RBF, cortical blood flow (CBF), pressure-dependent plasma renin activity (PRA) and pressure natriuresis in spontaneously hypertensive rats (SHR) by means of the combined (A/B) ET-receptor antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow probes and CBF by laser flow probes. During the experiments, the rats received an intrarenal infusion of either bosentan (1 mg/kg/h) or vehicle. Renal perfusion pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled electropneumatic device via an inflatable suprarenal cuff. Bosentan had no effect on resting RPP, CBF, PRA and renal sodium excretion, whereas RBF was lowered by 30% (p < 0.05). Furthermore after bosentan the rats revealed a complete loss of RBF autoregulation. In contrast no changes in autoregulation of CBF, pressure-dependent PRA and pressure natriuresis were observed. Our findings demonstrate a significant impairment in total RBF autoregulatory ability during renal ET-receptor blockade which is not confined to the cortical vessels. These data suggest that the renal ET system plays an important role in the dynamic regulation of renal blood flow in SHR.

ISSN:1420-4096    

DOI:10.1159/000174104

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

In this study we tested the hypothesis that mesangial cells participate in autoregulation of the glomerular filtration rate (GFR) in normotensive and hypertensive rats. Mesangial cell lesions were induced by intravenous administration of antithymocyte (anti-Thy 1.1) antibodies in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto rats (WKY). Normal murine serum was injected in control rats. Hemodynamic measurements were performed 24 h after the infusion of the anti-Thy 1.1 antibodies. Renal blood flow (RBF) was measured by a transit time flowmeter (Transonic) and the GFR was measured as the uptake of 125 iodine-labeled aprotinin (125I-Ap) by proximal tubular cells at the control renal arterial pressure and 131I-Ap at a pressure reduction close to the lower pressure limit of RBF autoregulation. RBF was unaltered and the autoregulatory capability was maintained in SHR and WKY after mesangial cell lesions. Mesangiolysis significantly reduced the total GFR in normotensive, but not in hypertensive animals. The fractional compensation of the GFR was attenuated in the outer cortical layer (p < 0.05) in normotensive WKY In SHRs the fractional compensation of the GFR was impaired in all cortical layers after mesangiolysis, slightly more in the outer than in the inner cortex. We conclude that mesangial cells may contribute to the autoregulation of GFR in hypertensive rats, but to a lesser extent in normotensive rats.

ISSN:1420-4096    

DOI:10.1159/000174105

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The aim of the present study was to investigate the role of renal nerves and atrial natriuretic factor (ANF) in the mechanisms responsible for the diuresis and antinatriuresis induced by morphine in rats in a normal state of hydration. Male Wistar rats weighing 350-400 g were divided into two groups: one group was subjected to bilateral renal denervation, whereas the other consisted of sham-operated controls. The animals were placed in individual metabolic cages, and morphine (1.25, 2.5, 5.0 or 10.0 mg/kg body weight) or vehicle (0.5 ml isotonic saline) was injected intraperitoneally. Urine was collected hourly for 1 h before and 3 h after morphine injection. The lower doses of morphine (1.25 and 2.5 mg/kg body weight) induced a transient increase in urine output (from 1.17 ± 0.12 to 2.49 ± 0.34 and from 0.78 ± 0.08 to 1.71 ± 0.18 µl/min, respectively). The diuretic response to these doses was similar in bilaterally denervated rats. Higher doses (5.0 and 10.0 mg/kg body weight) induced a marked but transient reduction in the urinary flow rate during the first hour (from 0.90+0.11 to 0.48+0.05 and from 1.37+0.17 to 0.45 ± 0.08 µl/min, respectively), followed by a delayed diuretic effect. The antidiuretic action of morphine was not observed in bilaterally denervated rats. In control rats, morphine induced a dose-dependent decrease in sodium excretion 1 h after administration, an effect that was blunted in the denervated group. The lower morphine doses (1.25 and 2.5 mg/kg body weight) elicited a transient increase in the glomerular filtration rate (GFR) in both control (from 1.23+0.12 to 1.67+0.17 and from 1.28+0.14 to 2.41+0.18 ml/min) and bilaterally denervated rats (from 1.29+0.14 to 1.66+0.17 and from 1.18+0.22 to 1.72+0.19 ml/min), whereas the higher doses (5.0 and 10.0 mg/kg body weight) produced a marked, transient GFR decrease in the controls (from 1.25+0.11 to 0.43 ± 0.05 and from 1.13+0.17 to 0.47 ± 0.08 ml/min) and bilaterally denervated animals (from 1.48+0.16 to 0.74 ± 0.09 and from 1.22+0.15 to 0.73 ± 0.06ml/ min), although the reduction was less pronounced with renal denervation. Morphine induced a transient, dose-dependent reduction in blood pressure (from 114+1 to 71 ± 6mm Hg at 10.0 mg/ kg body weight) and a dose-dependent elevation of plasma ANF. No differences in plasma ANF were observed between control and denervated animals under basal conditions (60 ± 7 vs. 42 ± 6 pg/ml) or after injection of 2.5 or 5.0 mg/kg of morphine (155+11 vs. 167 ± 9 and 360 ± 9 vs. 401+9 pg/ml, respectively). Our data suggest that the renal responses to intraperitoneal morphine administration derive from the integration of several different actions: (1) increased ANF release; (2) decreased arterial pressure; (3) subsequent activation of renal sympathetic activity, and (4) the direct effect of morphine on t

ISSN:1420-4096    

DOI:10.1159/000174106

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Platelet-activating factor (PAF) is an important mediator of injury in acute renal failure and glomerulonephritis. Intrarenal infusion of PAF reduces glomerular filtration rate and renal plasma flow and increases glomerular permselectivity via its renal hemodynamic and/or immunologic effects. Direct effects of PAF on glomerular capillary permeability are not known. We studied the direct effects of PAF on mesangial contraction (a measure of filtration area), glomerular capillary hydraulic conductivity (Lp) and capillary albumin permeability (Palbumin)· Glomeruli were isolated from Sprague-Dawley rats and incubated with or without various concentrations of PAF (10-9,10-7 and 10-5M) for up to 5 h at 370C. Mesangial contraction (percent change in glomerular volume) was assessed from the gradual decrease in volume of glomeruli during 20 min of incubation with PAF. Lp was calculated from the rate of change in glomerular volume during the 0.1 s of capillary expansion in response to a transcapillary oncotic gradient. Palbumin was calculated from a change in relative volume of glomeruli in response to an oncotic gradient. Mesangial contraction was maximal after 20 min of incubation and was concentration dependent (5.2+0.9, 7.9 ± 1.0 and 10.0+1.0%, respectively, with PAF 10-9,10-7 and 10-5M). Incubation of glomeruli with PAF 10-7M for 60 min at 37°C caused a significant decrease in Lp (2.25 ± 0.30 vs. control 3.12 ± 0.28 µl·min-1 •mm Hg-1 cm-1, n= 5). Palbumin of glomeruli incubated with PAF was unchanged up to 2 h but increased significantly with the highest concentration of PAF (10-5M) after 3 h of incubation (0.60 ± 0.18, n = 15, vs. control 0.00 ± 0.08, n = 20), whereas lower concentrations of PAF (10-7 or 10-9M) required at least 5 h of incubation with glomeruli to cause a significant increase in Palbumin (0.45 ± 0.09 and 0.48 ± 0.07, respectively, n = 15, vs. control 0.00 ± 0.08, n = 15). We conclude that PAF has multiple direct effects on glomerular functions, which are time dependent and may contribute to the altered capillary permeab

ISSN:1420-4096    

DOI:10.1159/000174107

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

In potassium-depleted rats lithium is reabsorbed by an amiloride-sensitive transport mechanism in the distal nephron segments, and the urinary fractional excretion of lithium (FELi) is reduced by almost 50% compared to that of potassium-replete rats. We have used renal clearance techniques to study the effects of adrenalectomy (Adx) or sham operation on amiloride-sensitive lithium reabsorption in conscious potassium-deprived (K5) and control (K200) rats. In the sham-operated rats, administration of a low potassium diet led to a significant reduction in FELi from 27.0 to 16.6% (p < 0.01), whereas in the Adx rats the reduction in FELi was smaller (from 27.0 to 22.6) and not statistically significant. Urinary sodium excretion was similar (1,100 nmol/min/100 g body weight) in all groups. During subsequent amiloride infusion in order to block the distal nephron reabsorption of lithium, urinary sodium excretion increased nearly twofold in the sham-operated groups whereas no change was evident in the Adx rats. Similarly, amiloride led to an increase in FELi in the sham-K5 group but failed to increase FELi in the Adx-K5 group. The results suggest that amiloride-sensitive lithium transport seen during potassium depletion is influenced by the presence of the adrenal glands, most likely due to their production of aldosterone.

ISSN:1420-4096    

DOI:10.1159/000174108

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Ciclosporin A (CsA) is a potent immunosuppressive agent which is extremely effective in controlling allograft rejection and in the treatment of autoimmune disease and nephrotic syndrome. Unfortunately, its use is limited by chronic, irreversible nephrotoxicity. Administration of CsA induces renal vasoconstriction, causing a reduction in renal blood flow. An alteration of the prostaglandin-thromboxane cascade may be involved in the vasoconstriction. We studied the role of thromboxane A2 in CsA nephrotoxicity and the ability of a thromboxane synthase inhibitor, OKY-046, to reduce the CsA nephrotoxicity. Daily administration of CsA 25 mg/kg for 28 days to Sprague-Dawley rats resulted in increased excretion of urinary thomboxane B2 (47.9+11.5 vs. 27.2 ± 9.7 ng/24h; p < 0.05) and decreased creatinine clearance (0.25 ± 0.07 vs. 0.43+0.17 ml/min/100g; p < 0.01) as compared with administration of vehicle only. Histologically, large numbers of lysosomes in the tubular epithelium were characteristic. Coadministration of OKY-046 prevented both the rise in urinary thromboxane B2 excretion (40.0 ± 11.8ng/24h) and the reduction in the creatinine clearance (0.44 ± 0.11 ml/min/100 g). The severity of the histological changes was significantly diminished. Selective inhibition of thromboxane production with OKY-046 may be valuable in the attenuation of CsA nephrotoxic

ISSN:1420-4096    

DOI:10.1159/000174109

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

To clarify whether the ovaries have a potential to attenuate the aggravating effect of testosterone (T) on glomerular injury, we investigated the effect of T in female rats with or without ovaries, using Adriamycin (ADR)-induced nephropathy in female Sprague-Dawley rats. Group 1 consisted of female control rats, group 2 received T, groups 3 and 4 were subjected to ovariectomy (OVX) at 5 weeks of age, and group 4 received further T treatment. Group 5 consisted of male control rats. T was injected subcutaneously every 4 weeks from 5 weeks of age through the end of the experiment. ADR 2 mg/kg was administered intravenously to all rats twice, at 8 weeks of age and 20 days later. Body weight, blood pressure, urinary protein and serum constituents were investigated every 4 weeks from 4 through 24 weeks after the second ADR injection. Each group was studied morphologically 24 weeks after the second ADR injection. Treatment with T or with OVX and T significantly increased the urinary protein excretion. OVX had no significant effect on the urinary protein excretion. Treatment with either T or OVX did not induce any significant effects on the renal function with regard to blood urea nitrogen (BUN), serum creatinine (Cr) and Cr clearance (Ccr) levels, but a combined treatment with OVX and T significantly lowered the serum albumin levels, increased the levels of BUN and Cr and lowered the Ccr values. The glomerulosclerosis index was significantly and markedly higher in control male rats than in control females. Treatment with T resulted in a slight but significant increase in glomerular injury to levels similar to those seen in ovariectomized rats. Combined treatment with OVX and T significantly aggravated glomerular injury in a somewhat accelerated manner, associated with a significant increase in glomerular tuft volume. Our results suggested that the ovaries could not completely suppress glomerular injury worsened by T administered at serum levels similar to those of male rats, but they had a potential to attenuate glomerular injury induced by T, and the protective effect of the ovaries on glomerular injury may be related to their attenuating effect on glomerular growth.

ISSN:1420-4096    

DOI:10.1159/000174110

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Hypercholesterolemic Imai rats spontaneously develop proteinuria and glomerulosclerosis, especially males. Estrogen attenuates the progressive glomerular injury in these male rats. To clarify whether this attenuating effect of estrogen depends on a reduction of testosterone and/or a reduction of the sex-related factors, we investigated whether testosterone administration eliminates the attenuating effect of estrogen on the development of glomerular injury in estrogen-treated male Imai rats. Estrogen significantly reduced sex-related low molecular weight protein excretion to undetectable levels; and treatment with estrogen and testosterone failed to increase these levels. Unexpectedly, treatment with estrogen and testosterone attenuated glomerular injury more than treatment with estrogen only. Estrogen significantly increased both levels of estrogen and growth hormone (GH), whereas it suppressed testosterone levels. Testosterone administration resulted in an increase in serum testosterone levels of about fivefold above the control levels, but reduced the elevated serum GH to the levels of the controls. These results suggest that estrogen appears to play a protective role by itself or in association with sex-related factors, independent of the levels of serum testosterone, and that testosterone does not exert its effect on augmenting glomerular injury and rather may act to attenuate glomerular injury associated with a reduction of GH levels.

ISSN:1420-4096    

DOI:10.1159/000174111

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The metabolic effects of an ammonium salt on the liver and kidney were investigated. Rats were allowed free access to a 0.28 M ammonium chloride (NH4CI) solution for 7- and 8-day periods. Serum urea concentration was significantly increased after 8 days of NH4Cl ingestion. However the following hepatic urea cycle enzymes remained unchanged: CPS, OTC, ASS and ASL. The pattern of urinary urea excretion was variable. When the data for the 7-day period were pooled, there was no significant difference between the control and acidotic groups. However, when they were examined on a daily basis, acidosis significantly decreased urea excretion on day 2. Urea excretion then began to increase, reached the control value on day 4 and was significantly greater than the control value on day 7. Urinary ammonium excretion of the acidotic group was significantly increased on day 2 and continued to rise throughout the 7-day period. Renal phosphate-dependent glutaminase of the acidotic group was significantly increased on the eighth day. These data indicate that NH4Cl ingestion alters the pattern of urea excretion in a manner not previously demonstrated.

ISSN:1420-4096    

DOI:10.1159/000174112

出版商:S. Karger AG    

年代:1997

数据来源: Karger