Obstructive jaundice and renal masses.

An 82-year-old patient with obstructive jaundice secondary to simple renal cyst also suffered pain and vomiting from partial duodenal obstruction. The symptoms were relieved by aspiration of 1,750 ml of fluid. This reaccumulated over a five-year period when aspiration again relieved his symptoms, which then only consisted of epigastric fullness. Review of the literature shows jaundice to be an extremely rare symptom of renal cyst.     

Role of the renin-angiotensin system on the parathyroid hormone-related protein overexpression induced by nephrotoxic acute renal failure in the rat

Parathyroid hormone-related protein (PTHrP), a mitogenic factor for renal cells, is overexpressed in acute renal failure (ARF). Recent data support an association between PTHrP and the renin-angiotensin system in the damaged kidney. The effects of angiotensin II (Ang II) inhibitors (quinapril, enalapril, and/or losartan) on PTHrP and the PTH1 receptor (PTH1R) expression in rats with either folic acid (FA)- or gentamicin-induced ARF were analyzed. The decreased renal function and the PTHrP upregulation and PTH1R downregulation induced by the nephrotoxins were inhibited by the Ang II blockers. In tubuloepithelial cells NRK-52E, the rapid (10 min) increase in PTHrP mRNA by FA, associated with a perinuclear relocalization of Ang II/AT1 receptor, was inhibited by losartan but not candesartan, which traps Ang II receptors at the cell surface. Maximal PTHrP protein overexpression by FA (at 24 to 72 h)-or by exogenous Ang II-was abolished by both Ang II antagonists. PTHrP upregulation by FA was preceded by increased extracellular signal-regulated kinase (ERK) phosphorylation and inhibited by the ERK inhibitor PD098059. FA also activated cAMP response element-binding (CREB) protein, and this was prevented by losartan in these cells. Moreover, PTHrP mRNA overexpression by either FA or Ang II occurred in NRK 52E that were transfected with a CREB construct but not the dominant-negative CREB133 construct. These findings demonstrate that the decreased renal function and PTHrP overexpression in nephrotoxin-damaged kidney depends on renin-angiotensin system. In this setting, intracellular Ang II/AT1 receptor recycling seems to be related to PTHrP induction through ERK and CREB activation in tubuloepithelial cells.     

Role of renal sympathetic nerve activity in renal failure associated with obstructive jaundice in the rat.

The propensity for renal failure associated with obstructive jaundice and liver disease may be related to enhanced vasoconstriction of the renal vascular bed with resultant decreases in renal blood flow. Renal sympathetic nervous activity may be a mediator of this effect. The increased renal production of prostaglandins which has been observed in previous models of bile duct ligation may serve to counterbalance the effects of such vasoconstricting influences. This study was undertaken to assess the effect of bile duct ligation on renal function and prostaglandin production in the rat. Furthermore, this study was designed to determine if renal sympathetic nerve activity contributes to the development of renal failure after bile duct ligation. Sprague-Dawley rats underwent either sham operation (n = 8), bilateral renal denervation (n = 10), bile duct ligation alone (n = 11), or bile duct ligation and bilateral renal denervation (n = 10). Renal function was assessed before and 4 days after operation. Bile duct ligation resulted in a 46% decrease in creatinine clearance (p less than 0.01), a 33% decrease in urinary sodium excretion (p less than 0.01), a twofold increase in urine flow (p less than 0.01), and twofold increases in urinary excretion of PGE2, 6-keto-PGF1 alpha, and thromboxane B2 (p less than 0.01). Renal denervation did not prevent the decreases in creatinine clearance and sodium excretion seen after bile duct ligation and had no effect on the changes in urine flow and prostaglandin excretion. These findings demonstrate that bile duct ligation in the rat results in impaired renal function, accompanied by increases in renal prostaglandin production. In addition, this study indicates that the perturbations in renal function and renal prostaglandin production induced by bile duct ligation are not mediated by renal sympathetic nerve activity.     

Interrelationships among the renin-angiotensin system, sympathetic nervous system and atrial natriuretic peptide in end-stage renal failure

Since it remains unclear how the regulatory mechanism of blood pressure and volume is associated with the renin-angiotensin system, the sympathetic nervous system, and atrial natriuretic peptide (ANP), we examined the changes in blood pressure and vasoactive hormones occurring in 12 patients with end-stage renal failure. They were divided into two groups, those who were anuric (group A, n = 7), and those who had a daily urine volume of more than 700 ml (group B, n = 5). The changes in the mean blood pressure (MBP) and these vasoactive hormones were observed during hemodialysis with water removal in group A and without water removal in group B, and during blood pressure reduction with sodium nitroprusside in group A. The basal levels of ANP in groups A and B were twice as high as those of normotensive subjects. During hemodialysis, MBP did not reveal any changes in both groups. In group A, ANP and body weight (BW) decreased, whereas the plasma renin activity (PRA) and norepinephrine (NE) increased. In group B, ANP remained stable during the first 3 hr and decreased at the end of hemodialysis. However, BW, PRA, and NE were unchanged. In group A, significant correlations were observed between the changes in BW and those in ANP (r = 0.52, p less than 0.05), PRA (r = -0.57, p less than 0.01), and NE (r = -0.76, p less than 0.01). During blood pressure reduction, MBP decreased with accompanying increases in NE and PRA. However, ANP did not show any change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pyrogenic renal hyperemia: the role of prostaglandins.

The intravenous administration of triple typhoid vaccine to anesthetized dogs resulted in a significant increase in renal blood flow accompanied by a modest decline in systemic blood pressure. This renal hyperemia was associated with elevated renal secretory rates of renin and prostaglandin E and F. Measurements of the intracortical distribution of radiolabeled microspheres revealed a progressive decrease in outer cortical blood flow rates and a progressive increase in inner cortical flow rates. When meclofenamate, an inhibitor of prostaglandin synthetase, was administered concomitantly with triple typhoid vaccine renal hyperemia did not develop. The renal renin secretory rate increased modestly and intracortical renal blood flow was not redistributed. The increased renal blood flow after triple typhoid vaccine administration to unanesthetized dogs was also reversed by meclofenamate. The marked increase in prostaglandin secretion by the kidney during renal hyperemia following triple typhoid vaccine administration (pyrogen), and the effect of meclofenamate, is consonant with a role for increased renal synthesis and release of prostaglandins.     

Pharmacokinetics and acute effect on the renin-angiotensin system of delapril in patients with chronic renal failure

The acute effect on the renin-angiotensin system and the pharmacokinetic properties of delapril, a new angiotensin converting enzyme inhibitor and its active diacid metabolites (delapril diacid and 5-hydroxy delapril diacid) arising from delapril in vivo were investigated in 4 hypertensive patients with chronic renal failure (CRF: 4 males, average age 49.5 (37-64) years, mean Ccr 22.2 ml/min/1.73 m2) and 9 patients with essential hypertension (EH: 6 males, 3 females, average age 42.8 (28-61) years, mean Ccr 79.3 ml/min/1.73 m2). In CRF, following a single dose of delapril hydrochloride (30 mg), the biological half lives (t1/2) of delapril diacid and 5-OH-delapril diacid were 4.69, 12.88 hours, the maximum serum concentration (Cmax) and the area under the plasma concentration-time curve ([AUC]24(0)) of delapril and its diacid metabolites were 414, 797 and 435 ng/ml, and 658, 6400 and 5068 ng X h/ml, respectively. In EH, the t1/2 of delapril diacid and 5-OH-delapril diacid were 1.21, 1.40 hours and the Cmax and [AUC]24(0) of delapril and its diacid metabolites were 489, 635 and 229 ng/ml, and 572, 1859 and 948 ng X h/ml, respectively. The [AUC]24(0) in CRF were significantly increased as compared with those in EH. The cumulative urinary excretions were significantly lower in CRF than in EH. The serum angiotensin converting enzyme (ACE) was markedly inhibited in both groups up to 24 hours. The plasma concentration of angiotensin II decreased in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of DNA damage in renal transplantation by losartan and enalapril: the role of renin-angiotensin system polymorphisms

Background In this study the effect of losartan and enalapril on the reduction of DNA damage was evaluated in regard to renin-angiotensin system (RAS) polymorphisms. Methods After determination of genotypes of RAS polymorphism by PCR, 64 renal transplant recipients were randomly allocated to one of four groups: the first and second groups were treated with E (E⁺: 10 mg/day) and L (L⁺: 50 mg/day) alone, respectively. The third group received E+L (E⁺L⁺: 10 + 50 mg/day), and the forth group received no medication (E⁻L⁻). The subjects were followed for 8 weeks. After a 2-week washout period, the E group changed to L and vice versa as a cross-over design. They were followed for another 8 weeks. Before and after treatment, we checked 8-OHdG and malondialdehyde (MDA) as biomarkers of DNA damage and lipid peroxidation, respectively. Results 8-OHdG levels were significantly decreased after treatment in the E⁺L⁺ and L⁺ groups (P < 0.001, P = 0.001, respectively). Only the TT genotype of AGT had the most antioxidative role regarding the treatment (P = 0.01). We found a remarkable correlation between MDA and DNA damage levels before and after intervention (r = 0.48, P < 0.001; r = 0.35, P = 0.006). Conclusion The protective effects of L⁺ and E⁺L⁺ on DNA breaks are surprising regarding the RAS polymorphisms.     

Long-term reduction of renal interstitial hydrostatic pressure after neonatal renin-angiotensin system inhibition in the rat

Background. Neonatal inhibition of the renin-angiotensin system (RAS) causes a decreased urinary concentrating ability, papillary atrophy, and tubulointerstitial inflammation long term. As a consequence of these morphological changes, we surmised that renal blood flow and renal interstitial hydrostatic pressure (RIHP) may be altered during and shortly after cessation of neonatal angiotensin-converting enzyme (ACE) inhibition, and that tentative changes of these variables would persist long after treatment withdrawal. Methods. Rats were given daily intraperitoneal injections of the ACE inhibitor, enalapril (10 mg/kg) or saline from days 3 to 23 postpartum, and the relationship between renal perfusion pressure (PP) and RIHP was investigated in 6- and 13-week-old anaesthetized rats. Results. Neonatal ACE inhibition did not affect baseline RIHP short term, whereas RIHP was reduced at 13 weeks of age versus controls (11.6±1.6 vs 18.5±1.0 mmHg, P<0.05). Changes in RIHP correlated positively to changes in renal PP, independent of treatment and age (slope averaged 0.11±0.03). Ongoing ACE inhibition until 6 weeks of age neither affected baseline RIHP nor altered the reactivity to changes in perfusion pressure. Mild renal histopathological abnormalities were present already 3 weeks after cessation of treatment and were aggravated significantly in the 13-week-old rats, showing a complete loss of the papillary parenchyma. Conclusion. The reduced baseline RIHP in adult rats seemed to constitute a functional correlate to the major papillary atrophy. However, RIHP responses to changes in renal perfusion pressure was maintained, possibly indicating a compensatory effect of the remaining vasa recta and/or peritubular capillary network. Taken together, lack of neonatal angiotensin II type-1 (AT1) receptor stimulation induces not only irreversible abnormalities of the renal architecture, but causes alteration of intrarenal haemodynamics, such as a reduced RIHP, which may have implications for the regulation of pressure-natriuresis.     

From mitochondria to disease: role of the renin-angiotensin system

Mitochondria are energy-producing organelles that conduct other key cellular tasks. Thus, mitochondrial damage may impair various aspects of tissue functioning. Mitochondria generate oxygen- and nitrogen-derived oxidants, being themselves major oxidation targets. Dysfunctional mitochondria seem to contribute to the pathophysiology of hypertension, cardiac failure, the metabolic syndrome, obesity, diabetes mellitus, renal disease, atherosclerosis, and aging. Mitochondrial proteins and metabolic intermediates participate in various cellular processes, apart from their well-known roles in energy metabolism. This emphasizes the participation of dysfunctional mitochondria in disease, notwithstanding that most evidences supporting this concept come from animal and cultured-cell studies. Mitochondrial oxidant production is altered by several factors related to vascular pathophysiology. Among these, angiotensin-II stimulates mitochondrial oxidant release leading to energy metabolism depression. By lowering mitochondrial oxidant production, angiotensin-II inhibition enhances energy production and protects mitochondrial structure. This seems to be one of the mechanisms underlying the benefits of angiotensin-II inhibition in hypertension, diabetes, and aging rodent models. If some of these findings can be reproduced in humans, they would provide a new perspective on the implications that RAS-blockade can offer as a therapeutic strategy. This review intends to present available information pointing to mitochondria as targets for therapeutic Ang-II blockade in human renal and CV disease.     

Protective role of furosemide and saline in radiocontrast-induced acute renal failure in the rat

Acute renal failure (ARF) can be produced in rats by a combination of insults which augment transport activity and blunt regulatory mechanisms designed to maintain medullary oxygen sufficiency. This type of ARF is characterized by necrosis of medullary thick ascending limbs (mTALs). Uninephrectomized, salt-depleted rats injected with indomethacin (10 mg/kg) develop ARF following the administration of the radiocontrast agent, iothalamate. Furosemide (20 mg/kg, intravenous), administered immediately before the contrast material, attenuated the severity of ARF and reduced mTAL necrosis. Treatment with furosemide and/or normal saline prevented both the decline in renal function and mTAL injury. It is concluded that furosemide and normal saline may ameliorate the course of ARF if administered before radiocontrast.     

L—精氨酸对阻塞性黄疸大鼠免疫功能的影响

本实验通过结扎大鼠胆总管建立阻塞性黄疸动物模型，将动物随机分成两组，实验组经口灌注Ｌ－精氨酸，每日１次共７天，对照组经灌注生理盐水，实验结果发现：实验组动物可增加胸腺指数，促进ＣｏｎＡ和ＬＰＳ诱导的大鼠脾脏淋巴细胞增殖反应，Ｌ－精氨酸对肝功能无损害。     

梗阻性黄疽引起肾脏功能衰竭机制的研究进展

梗阻性黄疽(obstructive jaundice,简称阻黄)是肝胆外科的常见疾病,由阻黄引起的肾脏功能衰竭(肾衰)由于其发病原因复杂,死亡率极高,已经越来越引起人们的重视.据报道阻黄病人术后总死亡率平均14%,肾衰的发生率为6%～8%[1],伴肾衰的阻黄病人病死率为68%～100%[2],可见如何防治阻黄术后发生急性肾衰,对于降低术后的病死率是非常重要的.     

肾素-血管紧张素系统在骨组织疾病中的作用

骨组织退行性疾病主要机制是成骨细胞活动减弱、破骨细胞活动增强,其病理表现为细胞外基质降解增加;骨肿瘤增生性疾病则表现为富血供效应。近年来,局部/组织肾素-血管紧张素系统(RAS)在介导骨退行性疾病和增生性疾病中的研究越来越多。该文就骨RAS及其抑制剂在骨质疏松、骨关节炎和骨肿瘤中的研究进展作一综述,并对骨RAS与椎间盘退变的潜在相关性作出展望。