Changes in renal hemodynamics and excretory function induced by a reduction of ANG II effects during renal development

The aim was to evaluate whether blockade of ANG II effects during renal development modifies the renal response to an increment of plasma amino acid concentration. It was also examined in anesthetized rats whether the reduction of the renal ability to eliminate an acute volume expansion (VE), elicited by blockade of ANG II during renal development, is sex and/or age dependent. Newborn Sprague-Dawley rats were treated with vehicle or an AT(1)-receptor antagonist (ARA) during postnatal nephrogenesis. Amino acid infusion induced increments (P < 0.05) of glomerular filtration rate (31 +/- 6%) and renal plasma flow (26 +/- 5%) in male but not in female vehicle-treated rats. Natriuretic and diuretic responses to amino acid infusion were similar in male and female vehicle-treated rats. These renal hemodynamics and excretory responses to amino acid infusion were abolished in ARA-treated rats. Renal responses to VE were evaluated at 3-4 and 9-10 mo of age in vehicle and ARA-treated rats. VE-induced natriuresis and diuresis were reduced by more than 38% (P < 0.05) in 3- to 4-mo-old male and female ARA-treated rats. An age-dependent reduction (P < 0.05) in the renal ability to eliminate VE was found in male but not in female rats treated with ARA. Our results demonstrate that the renal effects induced by an increment in amino acids are abolished when ANG II effects have been reduced during nephrogenesis. In addition, this reduction of ANG II effects elicits an impairment of the renal ability to eliminate an acute VE in males and females, which is aggravated by age only in male rats.     

Acute inhibition of the endogenous xanthine oxidase improves renal hemodynamics in hypercholesterolemic pigs

Hypercholesterolemia (HC), a major risk factor for onset and progression of renal disease, is associated with increased oxidative stress, potentially causing endothelial dysfunction. One of the sources of superoxide anion is xanthine oxidase (XO), but its contribution to renal endothelial function in HC remains unclear. We tested the hypothesis that XO modulates renal hemodynamics and endothelial function in HC pigs. Four groups (n = 23) of female domestic pigs were studied 12 wk after either normal (n = 11) or HC diet (n = 12). Oxidative stress was assessed by plasma isoprostanes and oxidized LDL, and the XO system by plasma uric acid, urinary xanthine, and renal XO expression (by immunoblotting and immunohistochemistry). Renal hemodynamics and function were studied with electron beam-computed tomography before and after endothelium-dependent (ACh) and -independent (sodium nitroprusside) challenge, during a concurrent intrarenal infusion of either oxypurinol or saline (n = 5-6 in each group). HC showed elevated oxidative stress, higher plasma uric acid (23.8 +/- 3.8 vs. 6.2 +/- 0.8 microM/mM creatinine, P = 0.001), lower urinary xanthine, and greater renal XO expression compared with normal. Inhibition of XO in HC significantly improved the blunted responses to ACh of cortical perfusion (13.5 +/- 12.1 and 37.2 +/- 10.6%, P = 0.01 and P = not significant vs. baseline, respectively), renal blood flow, and glomerular filtration rate; restored medullary perfusion; and improved the blunted cortical perfusion response to sodium nitroprusside. This study demonstrates that the endogenous XO system is activated in swine HC. Furthermore, it suggests an important role for XO in regulation of renal hemodynamics, function, and endothelial function in experimental HC.     

L-Arginine uptake affects nitric oxide production and blood flow in the renal medulla

Experiments were performed to determine whether L-arginine transport regulates nitric oxide (NO) production and hemodynamics in the renal medulla. The effects of renal medullary interstitial infusion of cationic amino acids, which compete with L-arginine for cellular uptake, on NO levels and blood flow in the medulla were examined in anesthetized rats. NO concentration in the renal inner medulla, measured with a microdialysis-oxyhemoglobin trapping technique, was significantly decreased by 26-44% and renal medullary blood flow, measured by laser Doppler flowmetry, was significantly reduced by 20-24% during the acute renal medullary interstitial infusion of L-ornithine, L-lysine, and L-homoarginine (1 micromol.kg(-1).min(-1) each; n = 6-8/group). In contrast, intramedullary infusion of L-arginine increased NO concentration and medullary blood flow. Flow cytometry experiments with 4-amino-5-methylamino-2',7'-difluorescein diacetate, a fluorophore reactive to intracellular NO, demonstrated that L-ornithine, L-lysine, and L-homoarginine decreased NO by 54-57% of control, whereas L-arginine increased NO by 21% in freshly isolated inner medullary cells (1 mmol/l each, n > 1,000 cells/experiment). The mRNA for the cationic amino acid transporter-1 was predominantly expressed in the inner medulla, and cationic amino acid transporter-1 protein was localized by immunohistochemistry to the collecting ducts and vasa recta in the inner medulla. These results suggest that L-arginine transport by cationic amino acid transport mechanisms is important in the production of NO and maintenance of blood flow in the renal medulla.     

Impaired renal functional reserve and albuminuria in essential hypertension

The stimulatory effects of an infusion of amino acids on glomerular filtration rate has previously been used to measure renal functional reserve and detect glomerular hyperfiltration. Thirty four patients with mild to moderate essential hypertension and seemingly normal renal function and 22 healthy controls were given infusions of amino acids to investigate whether renal functional reserve is reduced in essential hypertension and to detect patients at risk of renal damage. Although basal creatinine clearance increased after the infusion of amino acids in the controls (mean 27·9 ml/min; 95% confidence interval 18·2 to 37·6), the overall change was lower in the patients (mean 13·4 ml/min; 8·3 to 18·5), 11 of the 34 showing no increase at all. In these 11 non-responders the mean systolic blood pressure was higher than that in the 23 others (178·5 mm Hg v 157 mm Hg, respectively). Mean urinary albumin excretion was abnormal in the patients (93·3 mg/24 h; 44·2 to 142·4); eight of the 11 non-responders had an albumin excretion above the normal range (>20 mg/24 h). In the 11 patients without renal functional reserve a positive correlation was found between basal creatinine clearance and albumin excretion (r=0·695).As consumed renal reserve and albuminuria are markers of glomerular hyperfiltration studying renal function before and after infusion of amino acids can detect hypertensive patients at risk of progressive renal damage.     

Effect of felodipine on renal hemodynamics and excretion in the dog

The effects of felodipine on renal hemodynamics and excretion were evaluated in the anesthetized dog. Unilateral renal arterial infusion of felodipine produced ipsilateral increases in the absolute and fractional excretion of sodium and water which were greater than those of potassium; these effects occurred in the absence of changes in mean arterial pressure, renal blood flow, or glomerular filtration rate. There were no significant effects on renal hemodynamic or excretory function in the contralateral kidney. The unilateral renal arterial infusion of isotonic saline or vehicle produced no significant effects on renal hemodynamic or excretory function in either ipsilateral or contralateral kidney. Felodipine, a calcium antagonist with vasodilator antihypertensive properties, in doses which do not affect systemic or renal hemodynamics in the dog, increased urinary flow rate and sodium excretion by decreasing renal tubular water and sodium reabsorption. As a vasodilator antihypertensive agent, felodipine possesses potentially advantageous diuretic and natriuretic properties.     

Hemodynamic and renal effects of low-dose brain natriuretic peptide infusion in humans: a randomized,placebo-controlled crossover study

Brain natriuretic peptide (BNP) is a cardiac hormone with natriuretic activity. The aim of this study was to investigate the cardiovascular effects of pathophysiological levels of BNP on central hemodynamics, cardiac function, renal hemodynamics and function, and microvascular hemodynamics in healthy subjects. In this double-blind, placebo-controlled crossover study, we intravenously infused BNP (4 pmol. kg-1. min-1) or placebo for 1 h on two separate days in 12 healthy subjects (mean age, 60 +/- 5 yr). Nailfold and conjunctival capillary density, finger-skin (thermoregulatory) microvascular blood flow, and cardiac output were studied before and after infusion using intravital videomicroscopy, laser-Doppler fluxmetry, and echocardiography, respectively. Furthermore, during infusion, we measured the effective renal plasma flow and glomerular filtration rate using p-aminohippurate and inulin clearances. Blood pressure and heart rate were monitored for all measurements. Compared with placebo, BNP significantly decreased stroke volume with a tendency to decrease cardiac output. With subjects in the sitting position, mean arterial pressure decreased and heart rate increased after BNP infusion, whereas with subjects in the supine position, these variables remained unchanged. BNP increased natriuresis, diuresis, glomerular filtration rate, filtration fraction, and filtered load of Na+ compared with placebo, whereas effective renal plasma flow did not change. BNP did not affect the microvascular capillary density of conjunctiva and skin, microvascular blood flow, total skin oxygen capacity, and postocclusive recruitment. These results suggest that BNP has predominantly central and renal hemodynamic effects; however, it does not influence peripheral microcirculation in skin and conjunctiva.     

Blood pressure and renal hemodynamic responses to acute angiotensin II infusion are enhanced in a female mouse model of systemic lupus erythematosus

Inflammation and immune system dysfunction contributes to the development of cardiovascular and renal disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that carries a high risk for both renal and cardiovascular disease. While hemodynamic changes that may contribute to increased cardiovascular risk have been reported in humans and animal models of SLE, renal hemodynamics have not been widely studied. The renin-angiotensin system (RAS) plays a central role in renal hemodynamic control, and although RAS blockade is a common therapeutic strategy, the role of RAS in hemodynamic function during SLE is not clear. This study tested whether mean arterial pressure (MAP) and renal hemodynamic responses to acute infusions of ANG II in anesthetized animals were enhanced in an established female mouse model of SLE (NZBWF1). Baseline MAP was not different between anesthetized SLE and control (NZWLacJ) mice, while renal blood flow (RBF) was significantly lower in mice with SLE. SLE mice exhibited an enhanced pressor response and greater reduction in RBF after ANG II infusion. An acute infusion of the ANG II receptor blocker losartan increased RBF in control mice but not in mice with SLE. Renin and ANG II type 1 receptor expression was significantly lower, and ANG II type 2 receptor expression was increased in the renal cortex from SLE mice compared with controls. These data suggest that there are fewer ANG II receptors in the kidneys from mice with SLE but that the existing receptors exhibit an enhanced sensitivity to ANG II.     

Glomerulotubular balance, dietary protein, and the renal response to glycine in diabetic rats

The glomerular filtration rate (GFR) normally increases during glycine infusion, which is a test of "renal reserve." Renal reserve is absent in diabetes mellitus. GFR increases after protein feeding because of increased tubular reabsorption, which reduces the signal for tubuloglomerular feedback (TGF). Dietary protein restriction normalizes some aspects of glomerular function in diabetes. Renal micropuncture was performed in rats 4-5 wk after diabetes was induced by streptozotocin to determine whether renal reserve is lost as a result of altered tubular function and activation of TGF, whether 10 days of dietary protein restriction could restore renal reserve, and whether this results from effects of glycine on the tubule. TGF activation was determined by locating single-nephron GFR (SNGFR) in the early distal tubule along the TGF curve. The TGF signal was determined from the ionic content of the early distal tubule. In nondiabetic rats, SNGFR in the early distal tubule increased during glycine infusion because of primary vasodilation augmented by increased tubular reabsorption, which stabilized the TGF signal. In diabetic rats, glycine reduced reabsorption, thereby activating TGF, which was largely responsible for the lack of renal reserve. In protein-restricted diabetic rats, the tubular response to glycine remained abnormal, but renal reserve was restored by a vascular mechanism. Glycine affects GFR directly and via the tubule. In diabetes, reduced tubular reabsorption dominates. In low-protein diabetes, the vascular effect is enhanced and overrides the effect of reduced tubular reabsorption.     

Renal handling of amino acids in 5/6-nephrectomized rats: Stimulation of renal amino acid reabsorption after treatment with triiodothyronine or dexamethasone under amino acid load

Summary In anaesthetized adult female rats, the renal amino acid handling was measured six days after 5/6 nephrectomy (5/6NX). The distinct rise in blood urea nitrogen as well as the significant reduction in urine flow and GFR indicate an impairment of kidney function. In principle, in 5/6NX rats amino acid plasma concentrations were comparable to those of control animals with two intact kidneys, whereas the fractional excretions (FE_AA) of most endogenous amino acids measured were significantly enhanced. After bolus injection of leucine or taurine (each 20 mg/100 g b.wt.) or glutamine (90 mg/ 100 g b.wt.), dissolved in 2m1 normal saline per 100 g b.wt., the FE_AA of both the amino acids administered and the endogenous amino acids increased as a sign of overloaded amino acid reabsorption capacity. This effect was more pronounced in 5/6NX rats than in controls. As early as one hour after amino acid load, plasma concentrations and FE_AA returned to baseline values of 5/6NX rats. A pretreatment with triiodothyronine (20,µg/100 g b.wt.) or dexamethasone (60 µg/100 g b.wt.), both given intraperitoneally once daily for 3 days, stimulated the renal amino acid transport capacity in 5/6NX rats: the increase in FE_AA after amino acid load was significantly lower compared to non-pretreatred animals. This stimulation could be shown for the bolus amino acids and the endogenous amino acids and was more distinct in 5/6NX rats than in controls with two intact kidneys.     

Role of glomerular nitric oxide in glycerol-induced acute renal failure

Myoglobinuric acute renal failure remains one of the least understood clinical syndromes and the mediators involved remain obscure. The aim of the present study was to assess the role of nitric oxide in glycerol-induced acute renal failure under normal conditions and after uninephrectomy. Acute renal failure was induced in rats by injection of 50% glycerol (10 mL x kg(-1) body weight). Half of the animals were subjected to uninephrectomy two days before glycerol injection. Two days after the induction of acute renal failure, glomeruli from some animals were isolated and glomerular nitrite production was measured. Another group of animals was used for acute clearance studies. In this case, the effect of infusing either L-NAME or L-arginine was assayed. Glomerular nitrite production was significantly decreased in glycerol-induced acute renal failure. Glomeruli from uninephrectomized animals showed an increase in nitrite production, both in normal conditions and after glycerol injection, as compared with glomeruli from non-nephrectomized animals. L-NAME infusion worsened renal function in all the study groups, but more slowly in animals with glycerol-induced acute renal failure than in control rats. In uninephrectomized animals L-NAME reduced renal function more than in animals with two kidneys. In conclusion, in this model of acute renal failure the decrease in glomerular nitric oxide production plays an important role in the decrease in renal function. After uninephrectomy, an increase in glomerular nitric oxide synthesis plays a protective role against glycerol-induced acute renal failure.     

Relaxin-induced changes in renal sodium excretion in the anesthetized male rat

Pregnancy is associated with profound changes in renal hemodynamics and electrolyte handling. Relaxin, a hormone secreted by the corpus luteum, has been shown to induce pregnancy-like increases in renal blood flow and glomerular filtration rate (GFR) and alter osmoregulation in nonpregnant female and male rats. However, its effects on renal electrolyte handling are unknown. Accordingly, the influence of short (2 h)- and long-term (7 day) infusion of relaxin on renal function was determined in the male rat. Short term infusion of recombinant human relaxin (rhRLX) at 4 microg.h(-1).100 g body wt(-1) induced a significant increase in effective renal blood flow (ERBF) within 45 min, which peaked at 2 h of infusion (vehicle, n = 6, 2.1 +/- 0.4 vs. rhRLX, n = 7, 8.1 +/- 1.1 ml.min(-1).100 g body wt(-1), P < 0.01). GFR and urinary excretion of electrolytes were unaffected. After a 7-day infusion of rhRLX at 4 microg/h, ERBF (1.4 +/- 0.2 vs. 2.5 +/- 0.4 ml.min(-1).100 g body wt(-1), P < 0.05), urine flow rate (3.1 +/- 0.3 vs. 4.3 +/- 0.4 microl.min(-1).100 g body wt(-1), P < 0.05) and urinary sodium excretion (0.8 +/- 0.1 vs. 1.2 +/- 0.1 micromol.min(-1).100 g body wt(-1), P < 0.05) were significantly higher; plasma osmolality and sodium concentrations were lower in rhRLX-treated rats. These data show that long-term relaxin infusion induces a natriuresis and diuresis in the male rat. The mechanisms involved are unclear, but they do not involve changes in plasma aldosterone or atrial natriuretic peptide concentrations.     

Stimulation of renal amino acid reabsorption after treatment with triiodothyronine or dexamethasone in amino acid loaded rats

Summary In adult female anaestetized rats, the influence of triiodothyronine or dexamethasone on renal amino acid handling was investigated in leucine (20mg/100g b.wt.) or glutamine (45mg/100g b.wt.) loaded animals. Bolus injections of both amino acids were followed by temporary increase in fractional excretion of the administered amino acids as well of the endogenous amino acids which were not administered.Under load conditions (leucine and glutamine), dexamethasone treatment (60 g/100 g b.wt. for 3 days, i.p. once daily) was followed by a stimulation of renal amino acid reabsorption. The increase in fractional amino acid excretion after amino acid load was significantly lower than in untreated rats. The effect of triiodothyronine (20,g/1008 b.wt. for 3 days, i.p. once daily) was different in leucine and glutamine loaded animals: after leucine bolus injection a comparable stimulatory effect as shown for dexamethasone could be demonstrated, but after glutamine administration the stimulatory action of T3 was masked. T3 even increases fractional amino acid excretion in glutamine loaded rats as a sign of enhanced house-keeping in the renal tubular cells. These results confirm previous findings and indicate different effects of both hormones on the renal handling of amino acids.     

Cysteine enhances in vivo natriuretic potency of ethacrynic acid in the rat

Total renal blood flow, glomerular filtration rate, and renal excretory function were determined in anesthetized rats treated with intravenous infusion of ethacrynic acid, 0.36 mg.min-1.kg-1, alone or in combination with cysteine. Simultaneously, the corticomedullary electrolyte gradient was evaluated in vivo from measurement of tissue electrical admittance (reciprocal impedance). Renal hemodynamics was not altered by drug infusion. Sodium excretion increased 1.7-fold with ethacrynic acid alone and 5-fold after the addition of cysteine. Tissue electrolytes of inner medulla decreased much more in rats given ethacrynic acid plus cysteine. We conclude that the addition of cysteine to intravenous infusion of ethacrynic acid greatly enhances its in vivo natriuretic potency in the rat.     

Autoregulation of renal hemodynamics is not impaired by a 'physiologic' dose of glucagon

Glucagon has been suggested to be involved in the pathway by which protein and amino acids elevate renal blood flow (RBF) and glomerular filtration rate (GFR) postprandially. Recent data suggest that amino acids elevate RBF and GFR through an autoregulatory mechanism (i.e., by impairing renal autoregulation). If glucagon mediates the renal hemodynamic effects of amino acids, 'physiologic' infusion of glucagon would also be expected to impair autoregulation. We examined the effects of glucagon (5 ng/kg per min given intraportally and intravenously) on RBF and GFR autoregulation in anesthetized dogs. Intraportal glucagon (n = 6) increased RBF (24%) and GFR (23%) at normal arterial pressure. RBF and GFR were well autoregulated (greater than 90% of control) at renal arterial pressures greater than or equal to 85 mm Hg before and after glucagon. At 70 mm Hg, RBF and GFR decreased by 15 and 16%, respectively, before glucagon and by 19 and 22%, respectively, after glucagon. Intravenous glucagon (n = 6) produced similar effects. Intraportal glucagon at 500 ng/kg per min increased RBF (35%), heart rate (69%) and plasma glucose (78%) and decreased arterial pressure (16%) (GFR not measured). This dose impaired RBF autoregulation by 30%. The data suggest that a 'physiologic' dose of glucagon increases renal hemodynamics without impairing renal autoregulation. It is suggested that glucagon's vasodilatory effect on the renal vasculature may be additive to the renal effects of amino acids.     

Physiologic role for enhanced renal thromboxane production in murine lupus nephritis.

To investigate the physiologic significance of enhanced renal thromboxane production in murine lupus nephritis, we measured renal hemodynamics and eicosanoid production in MRL-lpr/lpr mice from 8 to 20 weeks of age. Over this age range, MRL-lpr/lpr mice develop an autoimmune disease with nephritis similar to human systemic lupus erythematosus (SLE). In these studies, glomerular filtration rate (GFR) and PAH clearance (CPAH) decreased progressively with age in MRL-lpr/lpr mice, but not in controls. This impairment of renal hemodynamics was associated with increased renal thromboxane production, as well as increased excretion of both thromboxane B2 (TxB2) and 2,3-dinor TxB2 in urine. There was an inverse correlation between renal thromboxane production in MRL-lpr/lpr mice and both GFR and CPAH. Furthermore, there were positive correlations between thromboxane production by the kidney and both the severity of renal histopathology and serum anti-DNA antibody levels measured in individual animals. Enhanced urinary excretion of TxB2 and the development of renal dysfunction also coincided temporally with the appearance of increased levels of interleukin 1 beta (IL-1 beta) mRNA in renal cortex. Acute administration of the specific thromboxane receptor antagonist GR32191 to MRL-lpr/lpr mice restored GFR to normal in early stages of the autoimmune disease. However, in animals with more advanced nephritis, the effect of acute thromboxane receptor blockade on renal hemodynamics was less marked. We conclude that thromboxane A2 is an important mediator of reversible renal hemodynamic impairment in murine lupus, especially in the early phase of disease.     

Acetylcholine chloride and renal hemodynamics during postnatal maturation in conscious lambs.

To test the hypothesis that acetylcholine-induced relaxation of the renal artery decreases with postnatal age, we measured parameters of renal hemodynamics before and for 35 s after aortic suprarenal injection of acetylcholine in conscious, chronically instrumented lambs aged approximately 1 wk (n = 5) and approximately 6 wk (n = 5). Acetylcholine was administered in one of five doses ranging from 0 to 10 mg/kg body wt; doses were administered randomly, in the same volume. There were significant age- and dose-dependent changes in renal vascular resistance after acetylcholine administration, such that the response was greater in 1-wk-old lambs. After the highest dose tested, renal vascular resistance decreased by 13.6 +/- 7.3 (SD) mmHg. ml(-1). min. g kidney wt in 1-wk-old lambs and by 9.1 +/- 3.2 mmHg. ml(-1). min. g kidney wt in 6-wk-old lambs at 35 s. We also observed a transient renal vasoconstriction before the renal vasodilatation in 6-wk-old lambs but not in 1-wk-old animals. These data provide the first age- and dose-dependent effects of exogenous administration of acetylcholine on renal hemodynamics during maturation in conscious animals.     

Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep

These experiments examined whether renal growth and the fetal renin-angiotensin system could be stimulated by infusion of amino acids and whether chronic amino acid infusions restored glomerulotubular balance, which had been disrupted during 4-h infusions. Five fetal sheep aged 122 +/- 1 days gestation received an infusion of alanine, glycine, proline and serine in 0.15 M saline at 0.22 mmol/min for 7 days. Six control fetuses were given saline at the same rate (5 ml/h). Kidney wet weights after amino acid infusion were 28% larger than control fetuses (P < 0.05), and renal angiotensinogen mRNA levels were approximately 2.6-fold higher (P < 0.005). Circulating renin levels and renal renin mRNA levels were suppressed (P < 0.05), and renal renin protein levels tended to be lower. Arterial pressure was increased, and there was a marked, sustained natriuresis and diuresis. Glomerular filtration rate and filtered sodium were approximately two-fold higher throughout infusion (P < 0.05). Fractional proximal sodium reabsorption, suppressed at 4 h (from 73.4 +/- 6.5 to 53.7 +/- 10.2%), did not return to control levels (36.1 +/- 3.4% on day 7, P < 0.05). Distal sodium reabsorption was markedly increased (from 79 +/- 25 to 261 +/- 75 mumol/min by day 7, P < 0.005), but this was not sufficient to restore glomerulotubular balance. The resultant high rates of sodium excretion led to hyponatremia and polyhydramnios. In conclusion, long-term amino acid infusions increased renal angiotensinogen gene expression, kidney weight, and distal nephron sodium reabsorptive capacity but failed to restore proximal and total glomerulotubular balance.     

Influence of triiodothyronine and dexamethasone on renal amino acid handling in rats loaded with various amino acid mixtures

Summary In adult female rats, the influence of dexamethasone or triiodothyronine on renal amino acid handling was investigated in amino acid loaded animals. Amino acids were administered intravenously as two mixtures, each containing four amino acids to overload amino acid reabsorption capacity. Bolus injections of both mixtures were followed by temporary increase in fractional excretion of the administered amino acids as well of the amino acids which were not covered in the mixtures. The administration of the two mixtures was followed by different interactions between various amino acid carriers.After dexamethasone pretreatment (60µg/100g b.wt. for 3 days, once daily) a stimulation of the renal amino acid handling could be shown. Triiodothyronine (20µg/100g b.wt. for 3 days, once daily) did not increase tubular reabsorption capacity for amino acids. It even increased fractional amino acid excretion in amino acid loaded rats as a sign of enhanced amino acid metabolism in the kidney and/or increased amino acid uptake into the tubular cells from the luminal site.     

葛根素对甘油致急性肾功能衰竭兔血液流变学和肾血流量的影响

目的 肌注甘油复制急性肾功能衰竭(ARF)兔模型,观察葛根素(Pue)对ARF兔血液流变学和肾血流量的影响.方法 健康雄性日本大耳白兔30只,随机分为正常组、ARF模型组、Pue 1组(20 mg/kg)、Pue 2组(40mg/kg)、Pue 3组(80 mg/kg).各组于不同时间点测量其肾血流量、血液流变学指标和肾功能指标(Cr、BUN),并观察肾组织形态学改变.结果 与模型组比较,Pue 2组和Pue 3组治疗后各时间点Cr、BUN降低(P＜0.05),血液流变学指标降低明显(P＜0.05),肾血流量增加差异具有统计学意义(P＜0.05).Pue 2组和Pue 3组肾小管上皮细胞肿胀减轻,管型少见.结论 葛根素可明显改善急性肾功能衰竭兔血液流变性,增加肾血流量,进而达到改善、减轻肾小管损害的作用.     

Effect of graded doses of naloxone on renal function in canine hemorrhagic shock.

All the parameters of renal function (inulin clearance, para amino hippuric acid clearance and urine flow) which were depressed during experimentally induced hemorrhagic shock in dogs improved significantly in addition to improvement in mean arterial pressure (MAP) after bolus administration (iv) of 1 or 2 mg/kg naloxone. A smaller dose (0.5 mg/kg) of naloxone, however, did not improve the renal function. Even renal arterial injection of the same dose of naloxone showed no improvement in the renal function. In both these cases the improvement in the MAP was significantly less as compared to other groups of animals which received 1 or 2 mg/kg naloxone. It may be concluded that (a) naloxone at doses of 1 or 2 mg/kg improved the renal function by improving MAP and (b) naloxone has no direct action on renal vasculature.