Decreased renal excretion of uric acid following diuretic administration in rats

The anti-ulcer effect of sofalcone, an isoprenyl chalcone derivative, on acetic acid-induced gastric ulcers in rats was studied histologically and histochemically. After administrations of sofalcone at 50 and 200 mg/kg twice daily for 10 days, contraction of the ulcer, mucosal regeneration, accelerated development of the collagen fibers in the granulation tissue at the base of the ulcer, and increase of acid mucopolysaccharides, an alcian blue stain-positive substance covering the regenerated mucosa, were noted. The healing effect of sofalcone was balanced in mucosal regeneration and connective tissue proliferation (formation of the collagen fibers). Sofalcone of 50 mg/kg showed a greater healing effect than gefarnate at the same dose and had a similar healing effect as L-glutamine at 200 mg/kg.     

噻嗪类利尿剂及氯沙坦对原发性高血压的血清尿酸水平的影响

目的：观察原发性高血压患者分别服用噻嗪类利尿剂、氯沙坦4周后血清尿酸的变化。方法：对在我院连续诊疗的原发性高血压患者128例随机分为利尿剂组和氯沙坦组,利尿剂组63例,氯沙坦组65例。结果：两组药物均能明显降低患者的血压,且两组降压幅度无明显差异。利尿剂组治疗后尿酸平均升高41．67umol/L（P〈0．01）,氯沙坦组平均下降30．47umol/L（P〈0．01）,两组药物治疗后尿酸之问的差异有显著性。结论：噻嗪类利尿剂会升高原发性高血压病患者尿酸水平,氯沙坦可降低原发性高血压患者的尿酸水平。     

Effects of uricosuric drugs and diuretics on uric acid excretion in oxonate-treated rats

A practical procedure for evaluating uricosuric agents was demonstrated using clearance experiments with potassium oxonate-treated rats. The fractional excretion value of uric acid showed a reabsorptive net flux of uric acid in the renal tubules of the animal, though the value was obviously higher than those of primates such as men, chimpanzees and cebus monkeys. However, the rats responded well to uricosuric drugs and diuretics. Probenecid and uricosuric diuretics such as tienilic acid induced hyperuricosuria due to the increase of fractional excretion of uric acid and/or the increase of the filtered amount of uric acid with the rise of plasma uric acid. On the other hand, furosemide had no effect on uric acid excretion at a low dose with moderate diuresis, while a higher dose decreased the fractional excretion of uric acid with elevation of plasma uric acid. Benzothiazides were also uricosuric at the lower doses, but the high dose, as in the case of the so-called uricosuric drugs, had no effect on the uric acid excretion and plasma uric acid level. Thus, oxonate-treated rats were useful for evaluating drug effects on uric acid excretion.     

Effect of combined vitamin E and insulin administration on renal damage in diabetic rats fed a high cholesterol diet

In the present study, we investigated the effects of a long-term treatment with vitamin E, an antioxidant vitamin, insulin, or their combination on renal damage in streptozotocin (STZ)-induced diabetic rats fed a high cholesterol diet. Increases in urinary albumin and lipid peroxide (LPO) excretions were observed in these diabetic rats, when both urinary parameters were measured at 8 and 15 weeks after STZ administration. Daily treatment with vitamin E, insulin, or their combination markedly suppressed the increase in the 24 h urinary albumin and lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules, fatty degeneration of glomerular endothelium and hypertrophy of glomeruli and mesangium were observed in the kidneys of the diabetic animals when histopathological evaluation was performed at 4, 8, and 15 weeks (glomerular and mesangial hypertrophy were observed only at 15 weeks). Combined vitamin E and insulin treatment was the most effective at suppressing these renal histopathological changes. These results indicate that combined vitamin E and insulin treatment additively prevents the development and progression of renal damage in diabetic rats. Possible mechanisms for the preventive effect of this combined treatment are discussed.     

Diurnal variation in serum uric acid of rats fed potassium oxonate

The uric acid plasma levels produced in rats fed a hyperuricemic diet including uric acid and potassium oxonate are highly variable and do not attain steady-state blood levels. The levels are dependent on the time of day that the blood was collected.     

Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers

Oxidative stress plays an important role in the development of atherosclerosis and contributes to tissue damage that occurs as a consequence, particularly in myocardial infarction and acute stroke. Antioxidant properties of uric acid have long been recognized and, as a result of its comparatively high serum concentrations, it is the most abundant scavenger of free radicals in humans. Elevation of serum uric acid concentration occurs as a physiologic response to increased oxidative stress-for example, during acute exercise-thus providing a counter-regulatory increase in antioxidant defenses. In view of its antioxidant properties, uric acid may have potentially important and beneficial effects within the cardiovascular system. We wished to investigate whether administration of uric acid was feasible and if it could have an impact on antioxidant function in vivo. We have, therefore, performed a randomized, placebo-controlled double-blind study of the effects of systemic administration of uric acid, 1,000 mg, in healthy volunteers, compared with vitamin C, 1,000 mg. We observed a significant increase in serum free-radical scavenging capacity from baseline during uric acid and vitamin C infusion, using two methodologically distinct antioxidant assays. The effect of uric acid was substantially greater than that of vitamin C.     

Effects of diltiazem on plasma uric acid level and renal uric acid excretion in rats

The effects of diltiazem on plasma uric acid level (PUA) and renal uric acid excretion were investigated in oxonate-loaded rats. Diltiazem (0.5 mg/kg, i.v.) decreased PUA without producing uricosuria, and it decreased fractional excretion of uric acid and renal blood flow. The present results suggest that diltiazem produces hypouricemia not accompanied by uricosuria, probably by affecting uric acid metabolism, and it may also cause an alteration in the renal handling of uric acid partly due to changes in renal hemodynamics.     

Effect of isoproterenol on renal uric acid excretion in rats

Effect of isoproterenol on renal uric acid excretion was examined in oxonate-loaded and oxonate-nonloaded rats, using a clearance technique. Oxonate loading was performed by continuous infusion into the femoral vein. Isoproterenol (50 micrograms/kg, i.v.) induced antidiuresis and hyperuricemia accompanied with decreases in urinary excretion rate of uric acid, uric acid clearance, inulin clearance, and uric acid clearance/inulin clearance ratio in oxonate-nonloaded rats. These effects of isoproterenol were inhibited by propranolol (1 mg/kg, i.v.). Very similar results were obtained in oxonate-loaded rats; i.e., systemic blood pressure decreased synchronously with uric acid excretion by isoproterenol. In contrast, phenylephrine (100 micrograms/kg, i.v.) induced hypertensive, diuretic and slightly uricosuric results. In allopurinol-pretreated and oxonate-loaded rats, isoproterenol also decreased renal uric acid excretion and showed a less potent hyperuricemic effect than that observed in the animals not pretreated with allopurinol. In addition, in rats with ligated renal vessels, the hyperuricemic effect of isoproterenol was completely inhibited by allopurinol. These results suggest that isoproterenol-induced hyperuricemia is related not only to the stimulation of uric acid production, but also to the depression of renal uric acid excretion.     

线粒体辅酶Q改善高脂饮食大鼠肾血流动力学的研究

目的探讨线粒体辅酶Q(MitoQ,Mitoquinone)对高脂饮食大鼠肾血流灌注的影响。方法 8周龄雄性SD大鼠30只,随机分成模型组(H组,n=10)、治疗组(HM组,n=10)和对照组(N组,n=10)。N组喂食基础饲料,H组、HM组喂食高脂饲料。9周后,HM组自饮水中加入MitoQ。三组大鼠继续喂养10周后进行肾脏声学造影检查,并检测大鼠血生化及肾组织丙二醛(MDA)含量,比较各指标的组间差异。结果与N组及HM组比较,H组大鼠肾皮质达峰时间(TTOP)延长,增强强度(A)及充盈速度(C)下降(P<0.01),总胆固醇(TC)、三酰甘油(TG)及低密度脂蛋白胆固醇(LDL-c)均明显增高(P<0.01),HM组与H组比较,以上各指标明显改善。H组血清及肾组织丙二醛(MDA)含量明显高于HM组及N组(P<0.01)。结论 MitoQ可降低机体内过氧化物含量,改善高脂饮食大鼠肾血流动力学状态。     

氨转运蛋白Rhbg和Rhcg在低蛋白饮食大鼠肾脏的表达

目的 观察氨转运蛋白Rhbg、Rhcg在低蛋白饮食大鼠肾脏集合管的表达.方法 利用蛋白印迹法和实时聚合酶链反应(PCR)分别检测低蛋白饮食组和正常对照组氨转运蛋白Rhbg和Rhcg在大鼠肾脏皮质、内髓、外髓的表达.结果 低蛋白饮食可以明显增加Rhbg在大鼠肾脏皮质的表达(P＜0.05),但不改变Rhcg在大鼠肾脏皮质、内髓和外髓的表达.结论 低蛋白饮食可能会改变氨转运蛋白在大鼠肾脏的表达.     

Lipid profile in mice fed a high-fat diet after exogenous leptin administration

Previous studies suggest a possible link between leptin and decreased lipid levels, however, the role of leptin in high-fat diet-induced hyperlipidemia remains unclear. The aim of our study was to evaluate the effect of administering leptin on plasma and tissue lipids in mice fed a high-fat diet. Feeding a high-fat diet (2% cholesterol, 0.125% bile salts, 5% peanut oil) to four-week-old healthy mice for a period of 45 days, resulted in significantly elevated levels of plasma and tissue total cholesterol, phospholipids, free fatty acids and triglycerides as compared with those of the control mice. Subsequently after thirty days, exogenous leptin (230 microg/kg i.p.) was administered simultaneously with the daily dose of high-fat diet every alternate day for fifteen days. Leptin administration significantly reduced the levels of total cholesterol, phospholipids, free fatty acids and triglycerides in the plasma, liver, heart and kidney of both the control and high-fat diet fed mice. Moreover, leptin administration markedly reduced the levels of plasma LDL, VLDL and elevated plasma HDL and the activity of lipoprotein lipase as compared with the untreated control and high-fat diet fed mice. Thus, leptin administration was found to have a marked protective effect against hyperlipidemia and thus obesity, by virtue of its lipid lowering effects.     

The effects of loading rats with intravenous isotonic sodium chloride on the renal response to diuretics

The effect of a number of diuretic agents was investigated on rats with different degrees of expansion of extracellular fluid volume. With moderate saline loading aminoisometradine and chlorthiazide were the most efficient diuretics. However, with a more severe saline load aminoisometradine and mersalyl had the greatest effect while chlorthiazide had no significant diuretic activity. The action of acetazolamide seemed independent of the saline load. Potassium chloride showed no diuretic activity. Injecting the drugs in pairs resulted in probable potentiation only with acetazolamide plus chlorthiazide. Since all the diuretics were used in doses which gave maximal effects, the summation of the effects of the other pairs of diuretics suggested different sites of action.     

Effects of angiotensin II receptor blockers on renal handling of uric acid in rats

Elevated serum uric acid level has been associated with increased cardiovascular risk in hypertensive patients. Several angiotensin II receptor blockers exhibit differential effects on regulation of serum uric acid level in humans. We have demonstrated that some angiotensin II receptor blockers trans-stimulate the uptake of uric acid by human URAT1 and others inhibit the transport of uric acid mediated by human URAT1, OAT1, OAT3 and MRP4 in vitro. This study investigated the effects of candesartan, pratosartan and telmisartan on renal handling of uric acid in rats in vivo and in vitro. Candesartan (0.1 mg/kg) significantly decreased the urinary excretion of uric acid and increased the plasma uric acid concentration. The kidney candesartan level after low-dose treatment is close to that required to trans-stimulate uric acid uptake in vitro. Pratosartan exhibited dose-dependent hypouricemic and uricosuric effects, while telmisartan showed no effects on plasma uric acid level. Furthermore, we confirmed the effects of the tested drugs on uric acid transport by rat renal brush border membrane transporter(s) and basolateral Oat1 and Oat3. Effects of angiotensin II receptor blockers in rats may be mainly determined by their intrinsic effects (cis-inhibition and trans-stimulation) on uric acid reabsorption transporter(s) and their pharmacokinetic properties in rats.     

槲皮素对尿酸性肾病大鼠肾损伤的作用机制研究

目的 基于槲皮素对尿毒素相关转运蛋白的调控规律,探讨其对尿酸性肾病大鼠肾损伤的作用机制.方法 通过每天灌胃给予100 mg·kg-1腺嘌呤、10％酵母粉饲料喂养构建尿酸性肾病大鼠模型.按照体重将雄性SD大鼠随机分为3组:正常组、模型组和槲皮素组,每组7只.槲皮素组大鼠在高嘌呤饮食基础上每日灌胃给予15 mg·kg-1槲...     

Hypotensive and uric acid-retaining effects of trichlormethiazide under dietary sodium restriction in spontaneously hypertensive rats

In order to evaluate both the hypotensive and uric acid-retaining effects of thiazide diuretics in an animal model with hypertension, the effects of trichlormethiazide were studied using spontaneously hypertensive rats (SHR) under dietary sodium restriction. Trichlormethiazide was dosed daily for two weeks at 0.05, 0.5, 3 and 10 mg/kg, p.o. All doses caused obvious natriuresis, while an increase of urine volume was observed only at 3 and 10 mg/kg. The hypotensive effect, which was estimated at day 6 and 13, was recognized at doses of more than 0.5 mg/kg. At the end of the dosing, the hematocrit value of all medicated groups rose, and both the uric acid excretory capacity, estimated by the clearance values of inulin and uric acid, and the plasma potassium level clearly decreased at 3 and 10 mg/kg. A detailed study using a dose of 3 mg/kg showed shifts of the cumulative sodium and potassium balances to negative directions against the control group. Thus, trichlormethiazide-treated SHR under dietary sodium restriction showed both a hypotensive effect which might be due to the natriuresis and a tendency toward undesirable side effects such as hypokalemia and hyperuricemia. As there is no practical method in animal studies for simultaneously proving hypotensive and uric acid-retaining effects of diuretic antihypertensives, the findings of the present study might aid in the evaluation of diuretics more useful than the thiazides.     

Effect of carvedilol on renal hemodynamics and renal excretory function in spontaneously hypertensive rats

The effects of the novel antihypertensive agent, carvedilol, on renal hemodynamics and excretory function have been investigated and compared with the effects of labetalol in conscious, spontaneously hypertensive rats. Sustained intravenous infusion of carvedilol or labetalol at a rate of 10 micrograms/kg/min resulted in a significant decrease in blood pressure which was equivalent in magnitude for both drugs. Carvedilol had no effect on renal hemodynamic parameters; glomerular filtration rate, renal blood flow, and filtration fraction were unchanged. In contrast, labetalol decreased the glomerular filtration rate by 13% (p less than 0.01) and the filtration fraction was reduced from 28 to 24%. Inasmuch as renal blood flow was unchanged and perfusion pressure was reduced, both compounds decreased renal vascular resistance. Urine flow decreased and osmolality increased with both carvedilol and labetalol. However, excretion of electrolytes was affected differently with the two compounds. While sodium and potassium excretion were significantly decreased with labetalol, sodium and potassium excretion remained stable during carvedilol infusion, which represents an important beneficial effect for a potent systemic vasodilator. We conclude, therefore, that carvedilol does not compromise the renal autoregulatory integrity in hypertensive rats, and that the antihypertensive activity of the compound is associated with an apparent 'renal sparing' effect, in that the decrease in blood pressure does not compromise the urinary excretion of sodium.