ROLE OF NITRIC OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION

1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension. 2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow. 3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate. 4. Studies were then undertaken to examine the long-term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible. 5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure.     

DIFFERENCES IN ENDOTHELIUM-DEPENDENT RELAXATION IN VARIOUS ARTERIES FROM WATANABE HERITABLE HYPERLIPIDAEMIC RABBITS WITH INCREASING AGE

1. Endothelium-dependent relaxation in response to acetylcholine (ACh) and the calcium ionophore A 23187 was examined in aorta, coronary, basilar and renal arteries isolated from Watanabe heritable hyperlipidaemic (WHHL) rabbits of 2, 6 and 12 months of age, with normolipidaemic heterozygous WHHL rabbits as controls. 2. In the rings of WHHL rabbit aortae and coronary arteries preconstricted with vasoconstrictors, endothelium-dependent relaxation in response to ACh was attenuated with age compared to the heterozygous WHHL rabbits. A significant negative correlation was found between the total cholesterol content and the relaxation response to ACh in the aortae or coronary arteries from 6 and 12 month old WHHL rabbits. 3. In the rings of basilar arteries, endothelium-dependent relaxations to ACh were not modified with age. Similarly, in the rings of renal arteries, the relaxation response to ACh was not changed with age, but in the 6 and 12 month preparations, after the age of 6 months, a contraction following the relaxation appeared at higher concentrations of ACh (10^?7 to 10^?6 mol/L). The contraction was endothelium-dependent and inhibited by indomethacin. 4. A 23187-induced endothelium-dependent relaxations were also markedly attenuated in the aorta and significantly in the coronary artery with age. 5. Endothelium-independent relaxation to sodium nitroprusside was not changed in all arteries from WHHL rabbits of different ages. 6. These findings indicate that in the aorta and coronary artery of the WHHL rabbit, the endothelium-dependent relaxation to ACh and A 23187 becomes impaired with increasing age (i.e., with the progression of cholesterol deposition in the arterial wall) but is preserved in the basilar and renal artery.     

VASOCONSTRICTION IN THE RENAL VASCULAR BED DURING EXERCISE: STUDIES IN CONTROL AND HEART FAILURE RABBITS

1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.     

重组人红细胞生成素治疗肾性贫血的临床分析

目的　观察重组人红细胞生成素 (RhEPO)对肾性贫血的治疗作用。方法　根据使用EPO剂量的不同将 39例慢性肾衰竭并血液透析病人分成 4组 ,观察治疗后 2、4、12个月时与治疗前 (0月 )相比红细胞数 (RBC)、红细胞比积 (Hct)及血红蛋白含量 (Hb)的变化。结果　 2 4例使用EPO10 0 - 15 0IU/ (kg·w) (6 0 0 0IU/w - 90 0 0IU/w) ,治疗后RBC、Hct、Hb较治疗前有显著升高 (P≤ 0 .0 0 1) ;5例使用EPO5 0IU/ (kg·w) (30 0 0IU/w) +间断输血患者 ,其RBC、Hct、Hb升高不显著 ;10例不用EPO而单纯输血患者 ,其RBC、Hct、Hb无明显变化 (P >0 .0 5 )。结论　EPO能较好地纠正肾性贫血 ;单纯输血不能治疗肾性贫血     

Clinicopathological study of vesicoureteral reflux (VUR)-associated pyelonephritis in renal transplantation

Abstract:  We retrospectively studied the occurrence of vesicoureteral reflux (VUR)-associated pyelonephritis using renal biopsies obtained from the transplanted kidneys, and correlated the histological changes with clinical parameters. Out of a total of 131 renal biopsies performed between 1990 and 2001 on renal transplant patients at the department of Urology of Nagasaki University Graduate School of Biomedical Sciences, 12 patients showed pyuria more than twice in a single year. Seven of these 12 patients were available for determining VUR by voiding cystourethrography (VCUG). Cystoureterography demonstrated VUR in three of seven studied patients with pyuria. A histopathological examination revealed dilatation of both proximal and distal tubules in renal biopsies of transplant patients with VUR, compared to renal biopsies of transplant patients without VUR, or non-transplanted patients with thin membrane disease. One of the patients with VUR showed advanced features of chronic pyelonephritis in four consecutive biopsies at different time points, suggesting a late stage of reflux nephropathy in the transplanted kidney. We conclude from our study that the occurrence of VUR-related pyelonephritis may be one of the important long-term complications in the survival of renal allografts.     

经皮肾穿气压弹道碎石联合体外冲击波碎石治疗上尿路结石

目的 探讨提高上尿路结石碎石成功率的微创治疗方法。方法 采用经皮肾穿微造瘘输尿管镜气压弹道碎石，术中放置双J管，术后配合体外冲击波碎石术(ESWL)治疗上尿路结石48例。结果 结石总排净率为89．1％，结石最小排净率79．2％，无严重并发症发生。结论 该方法结石排净率高，创伤较小，手术并发症少，是上尿路结石较为理想的微创治疗方法。     

Lipoprotein (a) levels in those with high molecular weight apo (a) isoforms may remain low in a significant proportion of patients with end-stage renal disease.

BACKGROUND: Studies have reported an increase in median Lipoprotein (Lp) (a) in patients with high molecular weight (HMW) apolipoprotein (apo) (a) isoforms and renal impairment. Some studies identify Lp (a) levels as a risk factor for vascular disease in renal failure whilst others have demonstrated an association with apo (a) isoform type and vascular disease. METHODS: A total of 239 patients at end-stage renal failure (ESRF) were studied prior to the initiation of dialysis. Blood was taken for Lp (a) levels and apo (a) isoforms. Clinical vascular disease (CVD) was assessed on the basis of clinical history and Rose questionnaire. The control group for Lp (a) levels consisted of 228 healthy volunteers. RESULTS: Despite a higher median Lp (a) level in those with HMW isoforms, 30% of patients had Lp (a) levels <10 mg/dl. Overall, 49% patients were identified as having CVD. Diabetes, smoking history and Lp (a) levels were significantly associated with CVD in logistic regression analysis, although when patients with low molecular weight (LMW) and HMW isoforms were analysed separately, Lp (a) levels were not significantly associated with CVD in those with LMW isoforms. The rates of CVD in those with HMW isoform and low Lp (a) levels were significantly lower than those with HMW isoforms and elevated Lp (a) levels, 34 vs 57% (P < 0.01). CONCLUSIONS: Although median Lp (a) levels in those patients at ESRF with HMW isoforms are higher than controls, in a third of such patients Lp (a) levels remain relatively low. These patients have lower rates of CVD than those with high levels of Lp (a).     

关木通引起慢性间质性肾炎7例报告

目的　观察关木通所致慢性肾损伤的临床和病理改变特点。方法　本组 7例中 ,男 5例 ,女 2例。 3例服关木通汤药 ,4例服含关木通成药。分析服用时间、累积总量与肾损害首发症状及症状出现时间、肾功能和肾病理改变的关系。结果　汤药组 :服药时间平均 3 3 3个月 ,累积总量平均 82 9 3 g ,首发症状为乏力 3例 ,夜尿增多 2例 ,平均时间为 8 3个月 ,Cr平均 40 2 μmol/L。肾病理 :3例均为重度寡细胞性肾间质纤维化 ,肾小管广泛萎缩。成药组 :服药时间平均 7 5个月 ,累积总量平均 13 6g ,乏力 3例 ,夜尿增多 1例 ,恶心呕吐、头痛头晕 1例 ,平均18 8个月 ,Cr 3 62 8μmol/L。肾病理为重度寡细胞性间质纤维化和灶状纤维化各 2例 ,肾小管灶状萎缩 3例 ,广泛萎缩 1例。结论　汤药组关木通积累大 ,发病时间早 ,肾病理改变重。提示关木通所致肾损其临床表现、病理改变与服用关木通时间、剂量相关。     

Hyperthyroidism associated with papilloedema and pyramidal tract involvement

Summary In a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS] who had normal mitochondrial enzyme activity, high doses of coenzyme Q₁₀ (CoQ) were administered. Clinical improvement with decreased serum lactate and pyruvate levels was observed. Though the mechanism of action of CoQ is not known, a trial is worthwhile in patients with MELAS.