Combination of Exercise and Enalapril Enhances Renoprotective and Peripheral Effects in Rats With Renal Ablation
Motoyori KanazawaTakeshi KawamuraL LIY. SasakiKenji MatsumotoHitomi KataokaOsamu ItoNaoki MinamiTokutaro SatoTetsuya Ootaka
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Abstract:
It is suggested that appropriate chronic exercise (EX) may produce improvements of the physical strength in patients with chronic renal failure (CRF). Because acute exercise causes proteinuria and decreases the renal blood flow and glomerular filtration rate, it is necessary to consider the influence of EX on renal function. Therefore, we assessed the renal and peripheral effects of moderate to intense EX as well as the effects of the combination of EX and enalapril (ENA) in a rat model of CRF.Male 5/6-nephrectomized Wistar-Kyoto rats were divided into six groups according to the following treatment: 1) no exercise (C); 2) ENA (2 mg/kg/day, subcutaneously); 3) moderate exercise with treadmill running (20 m/min for 60 min/day, 5 days/week) (EXm); 4) intense exercise with treadmill running (28 m/min for 60 min/day, 5 days/week) (EXi); 5) EXm+ENA; and 6) sham operation (S). The rats were then treated for 12 weeks.Both EX and ENA blocked the development of hypertension, blunted increases in proteinuria, reduced serum creatinine and blood urea nitrogen, and improved the index of glomerular sclerosis (IGS) and the relative interstitial volume of the renal cortex (RIV). Moreover, IGS and RIV in the EXm+ENA group were the lowest among all other nephrectomized groups. Furthermore, EXm+ENA enhanced capillarization as well as the proportion of type-I fiber in the soleus muscle.These results suggest that EX and ENA have renoprotective effects. The findings also suggest that EXm+ENA provided greater renoprotective effects than those of ENA alone, and that EXm+ENA had some additional peripheral effects without any complications in this rat model.Keywords:
Blood urea nitrogen
Glomerulosclerosis
Renal cortex
Objective:To observe the effect of Saponins of Panax Notoginseseng(PNS) on the accumulation of extracellular matrix(ECM) in renal cortex of nephrectomized rats(NXR) and to explore its renoprotective mechanism.Methods:Eight Wistar rats served as normal group,others rats of 5/6 NX were randomly divided into 4 groups:the model group,Bailing capsule group,the low-dosage PNS group and the high-dosage PNS group.Medicine was given to each group according to the designed concentration and dosage.The therapeutic course was 12 weeks.Proteinuria、renal function were measured,renal tissues were examined routinely by light microscope.The protein expression of type Ⅳ collagen(ColⅣ) and fibronectin(FN) in glomeruli were detected by ELISA,and MMP-2 activity and TIMP-2 protein expression in cortex were assessed with same methods respectively.Results:The proteinuria of the 5/6 NX rats was significantly reduced by PNS.The renal function was improved;renal pathological injuries,glomerulosclerosis and tublointerstitial fibrosis were relieved.TIMP-2 protein expression was markedly down-regulated,while MMP-2 activity was higher than that of the model group.The protein expressions of ColⅣ and FN were significantly inhibited.Conclusion:PNS may promote the degradation of ECM and ameliorate ECM accumulation in glomeruli through the activation of MMP-2 and the down-regulation of TIMP-2 protein expression in 5/6 NX rats.
Renal cortex
Glomerulosclerosis
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We determined the effect of intravenous and renal intra-arterial infusion of dopamine on the distribution of intracortical blood flow in kidneys of anesthetized dogs. Total renal and renal intracortical blood flows in dogs receiving dopamine intravenously were quantified by the radioactive microsphere technique with reference sampling. In dogs receiving dopamine by renal intra-arterial infusion, total renal and renal intracortical blood flows were determined from radioactive microsphere and electromagnetic flowmeter data. Tissue perfusion rates for the total kidney, the renal cortex, the renal outer cortex, and the renal inner cortex increased following either intravenous or direct renal intra-arterial infusion of dopamine. Dopamine infusion by either method caused a relative redistribution of renal blood flow from the outer twothirds to the inner one-third of the renal cortex. During direct dopamine infusion into the renal artery, no significant changes in renal hemodynamics occurred in the contralateral kidney. No changes in arterial blood pressure occurred during dopamine infusion by either method. These observations imply that the change in the fractional distribution of renal intracortical blood flow following dopamine infusion is not dependent on a systemic mode of action. This pattern of flow redistribution suggests that the intrarenal dopamine-specific receptor may be in higher number in the inner cortex or that the redistribution of cortical flow after dopamine infusion may reflect differing initial physiological states of the inner and outer cortical receptors for dopamine.
Renal cortex
PAH clearance
Renal circulation
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Objective:To investigate the effects of Pioglitazone on the expression of tumor necrosis factor-α(TNF-α)in the renal cortex of diabetic rats.Methods: SD rats were divided into three groups randomly: normal control group,diabetic group,and diabetic group with Pioglitazone treatment.At 8th week,blood glucose,HbA1c,u-Albumin,serum creatinine,urea nitrogen and TNF-αlevel in blood plasm were detected in three groups.the expression of TNF-αmRNA was detected in renal cortex by RT-PCR. Results: Blood glucose,glycosylated hemoglobin,urine micro albumin,serum creatinine,urea nitrogen and TNF-αlevel in blood plasm and the expression of TNF-αm RNA were all increased significantly in dialetic group compared with contol group,but they were much lower in diabetic group with Pioglitazone treatment. Conclusion: Pioglitazone could obviously reduce the expression of TNF-α in renal cortex of diabetic rats and it may protect the renal.
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Blood urea nitrogen
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Renal cortex
Contrast-enhanced ultrasound
Cardiac cycle
Renal circulation
Second-harmonic imaging microscopy
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The intrarenal hemodynamics of nine dogs were studied using 15 micron diameter plastic radioactive microspheres labeled with either 85Sr or 141Ce injected before and with the alternative isotope injected 30 minutes after the induction of sepsis. Total renal microsphere trapping increased by 30.6 per cent, p less than 0.01, after the induction of sepsis. The glomerular filtration rate was unchanged. Microsphere trapping in the outer and inner cortex increased by 36.9 per cent, p less than 0.005, and by 20.3 per cent, p less than 0.05, respectively, reflecting increased renal blood flow. Fractional renal microsphere distribution in the outer cortex increased from 70.0 to 73.4 per cent, p less than 0.01, following the induction of sepsis. These data confirm that sepsis results in renal vasodilatation. In addition, a shift in intrarenal blood flow to the outer cortex was demonstrated. Since the outer cortex is perfused with blood which first passes through the inner cortex, it can be hypothesized that renal blood flow in septic states may be passing through dilated glomerular vessels unable to trap microspheres in the inner cortex or passing through precapillary open arteriovenous shunts, or both, thereby bypassing inner cortical functioning glomeruli. This may partly explain the decreased renal function associated with increased renal blood flow in septic states.
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Repeated administration of cyclopenthiazide enhances renal PAH excretion in rats. In the 1st hr after an acute PAH load the renal excretion of PAH is doubled compared with controls. Haemodynamic measurements show that this acute PAH load is related to an increase in renal blood flow, in particular to a distinct increase in blood flow in the renal cortex. This increase in renal blood flow and in intrarenal blood distribution is higher than in stimulated rats. The increase in renal excretion of PAH is stimulated rats is not connected with an increase in renal blood flow. After an acute PAH load an additional increase in renal blood flow in stimulated rats could not be observed as compared with non stimulated control rats.
Renal cortex
PAH clearance
Renal physiology
Renal circulation
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Objective To explore the availability of ultrasound integrated backscatter(IBS) technique evaluation rabbit chronic renal failure(CRF) renal damage application value.Methods Fifteen healthy male rabbits were established the model of CRF and then different examinations were carried out at the last day of every two weeks(W2,W4,W6,and W8),with the data examined before the day of first injection as control(W0).Draw the values of IBS,the IBS%,serum creatinine(Scr) and blood urea nitrogen(BUN) and its kidney was removed for pathological examination by two-dimensional ultrasound techniques.Results ①After W2,the IBS% of the renal cortex began to increase significantly.After W2,the IBS% of renal cortex at each time point was statistically different,as compared with that at W0(P0.05).After W4,the IBS% of renal medulla began to increase significantly.After W4,the IBS% of renal medulla at each time point was statistically different,as compared with that at W0(P0.05).The changes of the IBS% of the renal cortex occurred earlier than those of renal medulla.②Two-dimensional ultrasonic examinations showed that the vertical diameter and anteroposterior diameter increased significantly.After W2 the values of both diameters at each time point were statistically different,as compared with those at W0(P0.05).③After W6,the level of serum creatinine and blood urea nitrogen began to increase significantly.The values examined were statistically different as compared with those at W0(P0.05).④Pathological changes were mainly found in the renal cortex at the early stage.These changes began at W2 and turned into worse significantly at W8.Conclusions During the development of chronic renal failure in rabbits,ultrasound integrated backscatter technology could reflect the pathological injuries of the kidney and provide more information for clinical monitoring and evaluating renal injuries during the development of CRF.
Renal cortex
Medulla
Blood urea nitrogen
Renal medulla
Chronic renal failure
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Sodium arachidonate, 10(-5) g/kg per minute, was infused into the renal artery of a nonfiltering canine kidney in situ in order to determine the effects of enhanced prostaglandin synthesis on renal blood flow and its distribution in circumstances where prostaglandins produced in the medulla could not gain access to the cortex via tubular fluid. The contralateral normal kidney was also infused with sodium arachidonate and served as control. Radioactive microspheres were used to calculate the hemodynamic effects. In the nonfiltering kidney, the total renal blood flow increased after sodium arachidonate from a mean of 105 ml/min per 100 g to 146 ml/min per 100 g (P less than 0.01). This increase was completely abolished by prior treatment with indomethacin, 8 mg/kg, intravenously. The normal kidney responded qualitatively the same as the nonfiltering side. In both kidneys, blood flow increased significantly to all cortical zones except the outermost (zone 1), but the fractional distribution of renal blood flow was significantly increased only in the innermost cortex (zone 4). Since the kidneys were nonfiltering, the increase of renal blood flow during infusion of arachidonic acid cannot be explained by prostaglandins being transported from renal medulla to the cortex through renal tubules. Most likely prostaglandins are produced locally in the cortex and have only local effects.
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Medulla
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In the present investigation prostaglandins (PGs) were determined in the renal cortex and the functional effects of the renal PGs on renal hemodynamics and on the renin-angiotensin system were evaluated. The levels of PGs, determined by mass fragmentography, were in the medulla: PGE2 4.36 +/- 1.04 mug/g and PGF2 alpha 1.6 +/- 0.50 mug/g and in the cortex: PGE2 0.19 +/- 0.04 mug/g and PGF2 alpha 0.21 +/- 0.07 mug/g. The unequivocal demonstration of PGs in the renal cortex forms a biochemical basis for a role of PGs in the regulation of renal hemodynamics and of the renin-angiotensin system.
Renal cortex
Plasma renin activity
Renal medulla
Medulla
Alpha (finance)
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1. We have studied the effects of two prostaglandin synthesis inhibitors on renal cortical blood flow distribution in conscious rabbits. 2. Renal blood flow distribution was estimated by means of radioactive microspheres injected into chronically implanted left atrial cannulae. Cardiac output was measured by a thermodilution technique. 3. Measurements were made in groups of animals treated with either indomethacin, meclofenamate or control injections of phosphate buffer. 4. A method of microtome slicing of the renal cortex was developed to standardize measurements. Microtome sections were grouped into inner, middle and outer zones. After both indomethacin and meclofenamate there was a reduction in total renal blood flow with a redistribution of flow from inner to outer cortex. 5. Estimated renal vascular resistance rose in all three cortical zones. 6. The data support the hypothesis that renal prostaglandin synthesis is necessary for maintaining flow to the deep cortex. It is suggested that renal prostaglandins may also influence flow in more superficial zones. 7. Estimated total systemic vascular resistance was increased both with meclofenamate and indomethacin, suggesting an inhibiting effect of prostaglandins on arteriolar tone throughout a major part of the systemic circulartion.
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