Renal function and glomerular hemodynamics in male endotoxemic rats

The renal effects of a single intravenous dose of two different E. coli lipopolysaccharides (LPS 0111:B4 and LPS 0127:B8), at the same dose of 100 micrograms/kg, were evaluated in euvolemic Munich-Wistar (MW) rats by whole kidney clearance techniques and micropuncture studies. Following LPS infusion, a significant decrease (8%) in mean BP was observed only in the LPS 0127:B8 treated group. Inulin clearance fell 57% (LPS 0111:B4), P less than 0.01, and 38% (LPS 0127:B8), P less than 0.01. Para-aminohippuric (PAH) clearance decreased 31% (P less than 0.01) and total effective renal vascular resistance rose 70% (P less than 0.03) in response to LPS 0111:B4. No significant change in PAH clearance was noted in the LPS 0127:B8 group. Superficial single nephron glomerular filtration rate (SNGFR) was reduced 69% (LPS 0111:B4), P less than 0.03, and 33% (LPS 0127:B8), P less than 0.02. Superficial glomerular plasma flow fell 48% (LPS 0111:B4), P less than 0.03, and 24% (LPS 0127:B8), P less than 0.03. Both lipopolysaccharides were associated with an increase in afferent arteriolar resistance (RA) which accounted for a reduction in the glomerular capillary hydraulic pressure (PGC). There was no change in the proximal tubular pressure in either group and, therefore, the net transcapillary hydraulic pressures were reduced. No measurable change in the ultrafiltration coefficient. Kf, was observed in either group. In a second set of protocols, the effect of prior administration of indomethacin or captopril on LPS 0111:B4 action was investigated. A significant decrease in BP occurred when animals were pretreated with captopril. Both indomethacin and captopril prevented the renal effects of LPS 0111:B4.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of smoking on systemic and intrarenal hemodynamics: influence on renal function

In recent years, it has become apparent that smoking has a negative impact on renal function, being one of the most important remediable renal risk factors. It has been shown clearly that the risk for high-normal urinary albumin excretion and microalbuminuria is increased in smoking compared with nonsmoking subjects of the general population. Data from the Multiple Risk Factor Intervention Trial indicate that at least in men, smoking increases the risk to reach end-stage renal failure. Smoking is particularly "nephrotoxic" in older subjects, subjects with essential hypertension, and patients with preexisting renal disease. Of interest, the magnitude of the adverse renal effect of smoking seems to be independent of the underlying renal disease. Death-censored renal graft survival is decreased in smokers, indicating that smoking also damages the renal transplant. Cessation of smoking has been shown to reduce the rate of progression of renal failure both in patients with renal disease and in patients with a renal transplant. The mechanisms of smoking-induced renal damage are only partly understood and comprise acute hemodynamic (e.g., increase in BP and presumably intraglomerular pressure) and chronic effects (e.g., endothelial cell dysfunction). Renal failure per se leads to an increased cardiovascular risk. The latter is further aggravated by smoking. Particularly, survival of smokers with diabetes on hemodialysis is abysmal.     

Renal function and hemodynamics during prolonged isoflurane-induced hypotension in humans

The effect of isoflurane-induced hypotension on glomerular function and renal blood flow was investigated in 20 human subjects. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and para-aminohippurate (PAH) clearance, respectively. Anesthesia was maintained with fentanyl, nitrous oxide, oxygen, and isoflurane. Hypotension was induced for 236.9 +/- 15.1 min by increasing the isoflurane inspired concentration to maintain a mean arterial pressure of 59.8 +/- 0.4 mmHg. GFR and ERPF decreased with the induction of anesthesia but not significantly more during hypotension. Postoperatively, ERPF returned to preoperative values, whereas GFR was higher than preoperative values. Renal vascular resistance increased during anesthesia but decreased when hypotension was induced, allowing the maintenance of renal blood flow. We conclude that renal compensatory mechanisms are preserved during isoflurane-induced hypotension and that renal function and hemodynamics quickly return to normal when normotension is resumed.     

Renal hemodynamics and glomerular morphology in repetitively pregnant aging rats

Measurements were made of renal and glomerular hemodynamics and glomerular morphology in repetitively pregnant and age-matched virgin female Munich-Wistar rats. Repetitive pregnancies and lactation provide a stimulus to chronic increases in glomerular filtration rate (GFR) and these rats were studied, by micropuncture, approximately 4 to 6 weeks after the end of the fifth gestation/lactation cycle. No differences were seen in GFR or renal plasma flow (RPF) rate nor in any of the determinants of single nephron filtration rate (SNGFR) in repetitively pregnant compared to virgin rats, although SNGFR itself was slightly but significantly elevated in repetitively pregnant rats. There was no evidence of systemic hypertension, proteinuria, or abnormal glomerular morphology in either group despite their advanced age (approximately 42 to 46 weeks). Thus, the moderate chronic increase in GFR due to the stimulus of repetitive pregnancy and lactation does not lead to eventual deterioration in renal function or structural abnormalities.     

Renal hemodynamics during pregnancy in chronically catheterized, conscious rats

Two types of experiments were performed, cross-sectional and longitudinal. In the cross-sectional studies, rats were mated, later prepared surgically, and then 5 or more days after surgery, each examined twice during days 11 to 15 or days 18 to 20 of gestation. Nonpregnant rats matched for age and prepregnant weight served as controls. In the longitudinal studies, rats were catheterized and, starting 6 days later, examined twice; then the same rats were mated and each was studied on days 5, 8, 12, 16, and 20 of gestation, as well as on day 5 postpartum. In the cross-sectional studies, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were elevated by approximately 26% and 20%, respectively, above nonpregnant controls at 11 to 15 days of gestation (GFR, 2739 +/- 94 vs. 2181 +/- 134 microliters . min-1, P less than 0.005; ERPF, 9367 +/- 295 vs. 7785 +/- 422 microliters . min-1, P less than 0.01). By 18 to 20 days of gestation, GFR and ERPF had returned to levels that were not significantly different from nonpregnant values. The longitudinal studies confirmed these findings in every respect and further revealed that GFR and ERPF were elevated above nonpregnant values as early as day 5 of gestation (P less than 0.005). Thereafter, they rose to peak values, at 12 and 16 days of gestation, of 3122 +/- 144 and 10,584 +/- 541 microliters . min-1, and then returned to nonpregnant levels by day 20 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estimation of the intrarenal hemodynamics in patients with primary aldosteronism

Intrarenal hemodynamics were estimated in patients with primary aldosteronism (PA) using the Gomez's equations and by analyzing their renal function curve. The study was performed in 6 patients with PA for 2 weeks; they were given a regular sodium diet (12-15 g/day) in the 1st week and a sodium restricted diet (1-3 g/day) in the 2nd week. Blood pressure and urinary sodium excretion (UNaV) were measured on the last three days of each stage. Glomerular filtration rate (GFR) and renal plasma flow rate (RPF) were also measured on the regular sodium diet. Afferent (RA) and efferent (RE) arteriole resistances, and glomerular hydrostatic pressure (PG) were calculated using Gomez's equations. UNaV was plotted on the ordinate as a function of mean blood pressure (MAP) on the x-axis. Assuming that the difference between MAP and the x-intercept of this renal function curve represents the effective filtration pressure, RA, PG and gross filtration coefficient of capillaries (KFG) were also calculated. GFR and RPF were 102 +/- 6, 469 +/- 27 ml/min, respectively. Estimated RA (6600 +/- 700 dyns.sec.cm-5) was markedly elevated, while RE (2500 +/- 100 dyns.sec.cm-5), PG (57 +/- 2 mmHg) and KFG (0.195 +/- 0.041 [ml/sec]/mmHg) remained normal. The intrarenal hemodynamic parameters obtained by analyzing the renal function curve were consistent with those by Gomez's equations. Recently, in DOCA-salt hypertension, an animal model analogous to human PA, PG has been reported to be increased, leading to renal damage. However, the increase in RA was as marked as seen in essential hypertension, and further the increase in PG was not observed in the patients of this study. Thus, it is not clear whether there is a meaningful relationship between glomerular hypertension and renal damage in PA as reported in DOCA-salt hypertension.     

Lung function, hypoxic and hypercapnic ventilatory responses, and respiratory muscle strength in normal subjects taking oral theophylline.

Methylxanthines are known to be respiratory stimulants and are thought by some to augment hypercapnic and hypoxic ventilatory drive and improve respiratory muscle strength. Hypoxic and hypercapnic ventilatory responses were measured in 10 normal subjects before, during, and after administration of theophylline for three and a half days. Pulmonary function, carbon dioxide production, and mouth pressures during maximal static inspiratory and expiratory efforts were also measured. The mean (SD) serum theophylline concentration was 13.8 (3.2) mg/l. Lung volumes and flow rates did not change significantly with theophylline. The mean (SD) values for maximum static inspiratory pressure were 152 (27), 161 (25), and 160 (24) cm H2O, respectively before, during, and after theophylline. Neither these values nor peak expiratory pressure measurements were significantly changed. The slopes of the hypercapnic ventilatory responses were 2.9 (0.9), 3.3 (1.2), and 3.3 (1.4) l/min/mm Hg carbon dioxide tension (PCO2) respectively before, during, and after theophylline administration. The respective values for the slopes of the hypoxic response were -1.4 (0.9), -1.3 (0.8), and -1.1 (0.9) l/min/1% oxyhaemoglobin saturation. None of these values changed significantly with theophylline. Theophylline, however, increased carbon dioxide production (200 to 236 ml/min) and alveolar ventilation (4.7 to 5.7 l/min) significantly, with a concomitant fall of end tidal PCO2 (35.5 to 32.9 mm Hg). It is concluded that in man oral theophylline at therapeutic blood concentrations increases carbon dioxide production and ventilation without changing pulmonary function, respiratory muscle strength, or the hypoxic or hypercapnic ventilatory response significantly.     

Measurement of hepatobiliary function and hepatic hemodynamics in portally hypertensive rats

Background

Portal hypertension induced by partial ligation of the portal vein (PPVL) is associated with cardiovascular changes including portal systemic shunting (PSS). Despite large diversion of portal blood, there are no reports on the effect of PPVL on hepatobiliary function. Here we report on the effect of PPVL on liver function.

Methods

Male Lewis rats were divided into 3 groups: control (n=10), PPVL (n=10) and bile duct ligated (BDL) (n=4). Under anesthesia, PPVL was performed around a 21-gauge needle and BDL was by ligation of the common bile duct. Under ether anesthesia, 0.1 mCi^99mTc-labelled Hepatoiodida^® was injected via the penile vein and scintigraphy performed. The heart and liver were chosen as regions of interest and the mean transit times for the heart (MTT_heart) and liver (MTT_liver) were calculated. PSS was measured by direct intraportal injection of⁵⁷Co-labelled microspheres.

Results

Portal pressure was significantly elevated in the PPVL group (p<0.001 vs. control) and PSS was in evidence (24±15%, SD, p<0,001). The MTT_heart and MTT_liver for the control group (97±12 sec and 357±49 sec, respectively) were not significantly different than those for the PPVL group (150±50 sec and 410±48 sec, respectively). In the BDL group, the MTT_heart and MTT_liver were significantly different from control and PPVL.

Conclusions

We conclude from our results that despite the presence of significant PSS, no change in hepatobiliary function in rats with prehepatic portal hypertension occurs.     

Renal papillary morphology and intrarenal reflux in the young pig

Intrarenal reflux in piglets has been related to the morphology of individual renal papillae. These studies show that intrarenal reflux occurs only in the presence of the more extensively fused papillae found predominantly at the upper and lower poles of the kidney. These papillae each have a flattened or concave area cribrosa with large open papillary ducts which cannot be closed by a rise in intracalyceal pressure. In contrast intrarenal reflux never occurs into cone-shaped papillae seen most commonly in the mid-zone of the kidney, which have easily closed, oblique, slit-like papillary duct orifices. The significance of these findings in relation to the genesis of chronic pyelonephritic scarring is discussed.     

Intrathecal dexmedetomidine attenuates hypercapnic but not hypoxic cerebral vasodilation in anesthetized rabbits

BACKGROUND: Systemic dexmedetomidine (DXM) attenuates the cerebral vasodilation induced by hypercapnia and decreases the cerebral blood flow response to hypoxia. We determined whether lumbar intrathecal DXM affected the cerebrovascular reactivity to hypercapnia and hypoxia. METHODS: Rabbits (n = 55) anesthetized with pentobarbital were prepared for measurement of pial vessel diameters using a closed cranial window preparation. The first study evaluated the response to hypercapnia after intrathecal administration of DXM (2 microg/kg; n = 7) or normal saline (n = 8). The second evaluated the response to hypercapnia after intrathecal DXM in the presence of yohimbine (20 microg/kg followed by DXM 2 microg/kg; n = 7). The third evaluated the response to mild or moderate hypoxia after intrathecal DXM (2 microg/kg; n = 7) or normal saline (n = 7). The hypercapnic responses were also examined in the presence of systemic DXM (2, 10 microg/kg; n = 6), topical DXM (10-8 m, 10-6 m; n = 6) and of intrathecal clonidine (2 microg/kg; n = 7). RESULTS: The pial arteriolar dilator response to hypercapnia was significantly attenuated after intrathecal administration of DXM. Pretreatment with yohimbine completely blocked the decreased reactivity to hypercapnia. Intrathecal clonidine, although less than DXM, also attenuate the hypercapnic response. Intrathecal DXM did not affect the vasodilation of pial arterioles induced by mild or moderate hypoxia. The systemic DXM 10 microg/kg and topical DXM 10-6 m, but not systemic 2 microg/kg and topical 10-8 m, attenuated hypercapnic vasodilation of pial arterioles. CONCLUSIONS: The presence of alpha2-adrenoceptor agonist administered intrathecally into the lumbar spinal region attenuates hypercapnic but not hypoxic cerebral vasodilation, probably via a stimulation of central alpha2-adrenergic receptors of the central nervous system.     

Renal ischemia in rats: mitochondria function and laser autofluorescence

Ischemia-reperfusion injury is the major cause of organ dysfunction or even nonfunction following transplantation. It can attenuate the long-term survival of transplanted organs. To evaluate the severity of renal ischemia injury determined by histology, we applied laser- (442 nm and 532 nm) induced fluorescence (LIF), mitochondria respiration, and membrane swelling to evaluate 28 Wistar rats that underwent left kidney warm ischemia for 20, 40, 60, or 80 minutes. LIF performed before ischemia (control) was repeated at 20, 40, 60, and 80 minutes thereafter. We harvested left kidney tissue samples immediately after LIF determination for histology and mitochondrial analyses: state 3 and 4 respiration, respiration control rate (RCR), and membrane swelling. The association of optic spectroscopy with histological damage showed: LIF, 442 nm (r2 = 0.39, P < .001) and 532 nm, (r2 = 0.18, P = .003); reflecting laser/fluorescence-induced, 442 nm (r2 = 0.20, P = .002) and 532 nm (r2 = 0.004, P = .67). The associations between mitochondria function and tissue damage were: state 3 respiration (r2 = 0.43, P = .0004), state 4 respiration (r2 = 0.03, P = 0.38), RCR (r2 = 0.28, P = .007), and membrane swelling (r2 = 0.02, P = .43). The intensity of fluorescence emitted by tissue excited by laser, especially at a wave length of 442 nm, was determined in real time. Mitochondrial state 3 respiration and respiratory control ratio also exhibited good correlations with the grade of ischemic tissue damage.     

Renal function and oxygen consumption during bacteraemia and endotoxaemia in rats

Background: The hypothesis that renal failure during septic shock may occur as a result of hypoxia-related cell dysfunction was investigated in two rat models of distributive shock. Method: Pentobarbitone-anaesthetized rats received either a bolus (1 ml) of living Escherichia coli bacteria (hospital-acquired strain, 1 x 10x⁹ CFU/ml; BA-group, n=7), or a 1-h infusion of endotoxin (E.coli O127.B8: 8 mg/kg; ET-group, n=7). Results: Urine flow in the BA- and ET-group reached a nadir at 1 h but thereafter increased and reached values higher than control at 3 h. At this time point, renal oxygen delivery had decreased, in the BA-group mainly due to a fall in arterial oxygen content and in the ET-group to a fall in renal plasma flow (clearance of ¹³¹I-hippurate). However, renal oxygen extraction had significantly increased, by 31% in the BA and by 59% in the ET group, while renal oxygen consumption remained the same. Net tubular sodium reabsorption had decreased by 55% in the BA and by 25% in the ET group, due to a fall in glomerular filtration rate (clearance of creatinine). Hence an excess oxygen consumption was found which was caused neither by an increased renal glucose release nor by the presence of an increased number of leukocytes stuck in the glomeruli. Renal tubular cells showed normal morphology. An indication that proximal tubular function in the BA and ET group remained largely intact were normal ATP levels, absence of urinary glucose, and a normal fractional excretion of sodium. However, since urine flow had increased in shocked rats at 3h, water appeared selectively lost. Conclusion: Our data indicate that in rat models of septic shock renal failure is not caused by cortical hypoxia or a shortage of cellular energy supply.     

Renal function and urinary prostaglandins in rats given an adenine diet

The glomerular filtration rate (GFR), renal plasma flow (RPF) and renal blood flow (RBF) were all markedly decreased in rats given an adenine diet as the period of adenine administration lengthened. Concurrently, the urinary excretions of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha(6-keto-PGF1 alpha) decreased gradually in parallel with the renal function parameters, whereas the urinary excretion of thromboxane B2 (TXB2) increased markedly. These findings suggest the involvement of prostaglandin in the renal circulation.     

低氧环境下异丙酚对新生大鼠学习记忆功能的影响

目的 探讨低氧环境下异丙酚对新生大鼠学习记忆功能的影响.方法 健康SD大鼠84只,日龄7 d,按照随机数字表法分为6组(n=14):异丙酚低氧组(PH组)、异丙酚空气组(PA组)和异丙酚纯氧组(PO组)分别腹腔注射异丙酚50 mg/kg,1次/d,连续7 d;生理盐水低氧组(CH组)、生理盐水空气组(CA组)和生理盐水纯氧组(CO组)腹腔注射生理盐水5.0 ml/kg,1次/d,连续7 d.每次注射完毕后分别放于低氧(18%O2)、空气和纯氧环境中.记录给药后SaO2和RR,待翻正反射恢复后放回鼠笼.于第7天注射完毕后24 h,各组随机取6只大鼠,取脑组织,观察海马神经元凋亡情况.其余大鼠于给药后2周进行Morris水迷宫实验,测试学习记忆功能.结果 与CO组比较,PO组RR降低,T1.2时逃逸潜伏期延长(P＜0.05);与CA组比较,PA组RR和SaO2降低,凋亡指数升高,逃逸潜伏期延长,穿越原平台区次数减少(P＜0.05);与CH组比较,PH组RR和Sa02降低,凋亡指数升高,逃逸潜伏期延长,穿越原平台区次数减少(P＜0.05);与PO组比较,PA组和PH组SaO2降低,凋亡指数升高,逃逸潜伏期延长,穿越原平台区次数减少(P＜0.05).CO组、CA组和CH组上述各指标差异无统计学意义(P＞0.05).结论 在低氧环境下,异丙酚可诱发新生大鼠海马神经元明显凋亡,降低学习记忆功能.