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H H Neumayer

Publications and source records attributed to H H Neumayer.

At least 91 records · Page 5Linked to original sources
PubMed1998

Pathophysiology in endothelin-1 transgenic mice.

Transgenic mice expressing the human endothelin-1 (ET-1) were generated. These mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension. Consequently, a progressive decrease in renal blood flow and/or glomerular filtration rate was observed, demonstrated by altered creatinine clearance and by magnetic resonance imaging. These genetically altered transgenic mice provide an interesting animal model in which to elucidate the role of ET-1 in the modulation of renal hemodynamics and glomerular and tubule functions.

Animals↗
PubMed1998

Renal endothelin system in diabetes: comparison of angiotensin-converting enzyme inhibition and endothelin-A antagonism.

An activated renal endothelin (ET) system is implicated in the pathogenesis of renal fibrosis, as recently shown in ET-1 transgenic mice. Because progressive renal fibrosis is also a major finding in diabetic nephropathy, we analyzed the activity of the renal ET system in rats with streptozotocin-induced diabetes mellitus and the effect of blocking the ETA receptor, using the orally active ETA antagonist LU 135252. The effects of long-term treatment with LU 135252 were compared with those of an ACE inhibitor. Plasma and urinary ET-1 concentrations were measured. Progression of diabetic nephropathy was analyzed by measuring urinary albumin and protein excretion. Urinary ET-1 excretion was significantly elevated as early as 7 days after induction of diabetes and increased further. The daily urine volume was significantly correlated with urine ET-1 excretion. Treatment with LU 135252 significantly decreased the ET-1 excretion by more than 50%, whereas ACE inhibition resulted only in a mild decrease. Albumin excretion was significantly decreased after ACE inhibition, whereas ETA inhibition resulted in a nonsignificant decrease. Urinary ET and albumin excretion probably reflect independent mechanisms of renal damage in diabetes.

Albuminuria↗
PubMed1998

Renal endothelin system in polycystic kidney disease.

Polycystic kidney disease (PKD) is characterized by interstitial fibrosis and formation of renal cysts. Interestingly, interstitial fibrosis and renal cyst formation were also seen in human endothelin-1 (ET-1) transgenic mice. This study, therefore, analyzes the tissue distribution of ET-1, the tissue concentrations of ET-1, as well as the expression of ET receptor subtypes in the kidneys of a rat model of PKD: Han:SPRD rats. Six-week-old heterozygous (cy/+) and homozygous (cy/cy), as well as 6-mo-old heterozygous (cy/+) Han:SPRD rats and the corresponding age-matched Sprague Dawley littermates (SD) (+/+) were analyzed. Furthermore, the acute effects of the mixed (A/B) endothelin receptor antagonist bosentan on hemodynamic and renal function were investigated in 6-mo-old, conscious, chronically instrumented (cy/+) rats. The kidneys of affected rats showed significantly elevated tissue levels of ET-1 compared with age-matched controls (3.5 +/- 0.3-fold in young cy/cy rats, P < 0.01; 1.4 +/- 0.2-fold in young cy/+ rats, P < 0.01; 6.2 +/- 0.4-fold in old cy/+ rats, P < 0.001) due to a highly increased ET-1 synthesis within the epithelial cells of the cysts. Analyzing tissue sections from patients with typical autosomal dominant PKD demonstrated a high ET-1 expression within the epithelial cells of the cysts as well. Scatchard analysis revealed a markedly decreased ETA and ETB receptor density in all groups of affected rats. The acute blockade of both endothelin receptor subtypes using bosentan in 6-mo-old heterozygous PKD rats led to a significant decrease in mean arterial BP (MAP) (-19.7 +/- 2.1 mmHg, P < 0.05) and GFR (-41 +/- 5%, P < 0.005). Renal blood flow (RBF) was significantly increased (+2.1 +/- 0.5 ml/min, P < 0.05) after bosentan, whereas bosentan had no effect on MAP, GFR, and RBF in age-matched controls. These data show that the paracrine renal endothelin system is activated in PKD and participates in the regulation of MAP, GFR, RBF, and possibly contributes to renal cyst formation and fibrosis.

Analysis of Variance↗
PubMed1998

Pharmacokinetics of mycophenolate mofetil in renal transplant recipients on peritoneal dialysis.

Little is known about the pharmacokinetics of mycophenolatic acid (MPA) in the early posttransplant period after renal transplantation. We studied the impact of peritoneal dialysis on the pharmacokinetics of MPA in 5 patients following renal transplantation (3-6 weeks after transplantation). Three patients had a glomerular filtration rate (GFR) of less than 10 ml/min, 1 patient had a GFR of 32, and 1 of 58 ml/min. Pharmacokinetics of MPA and its main metabolite mycophenolic acid glucuronide (MPAG) were studied on 2 consecutive days (12-hour intervals: with and without peritoneal dialysis). Dosing of MPA was 2 x 1 g/day. MPA and MPAG concentrations were determined by HPLC methods. After initiation of peritoneal dialysis in patients with severe renal impairment (GFR < 10 ml/min) MPA area under the concentration curve (AUC) decreased substantially (15-59%). The calculated clearance of MPA was higher (14.6 vs 8.1 ml/min/kg) on the day of peritoneal dialysis than during the dwell-free day. MPAG-AUC decreased up to 26% in these patients. In both patients with a GFR > 30 ml/min we observed an increase of MPA-AUC on the day of peritoneal dialysis and a decreased MPA clearance. MPAG-AUCs remained stable. Patients with a reduced GFR had much higher MPAG values than patients with a GFR 30 ml/l, however, we did not observe any differences for the MPA levels. We found a significant inverse correlation between GFR and MPAG-AUC (r = 0.91, p < 0.05). While MPA was found only in traces in the peritoneal ultrafiltrate, the cumulative amount of MPAG removed by peritoneal dialysis reached up to 2 g per 12 hours, representing up to 1.2 g of MPA. This is the first report describing a reduction of MPA- and MPAG-AUC during peritoneal dialysis. Further studies are needed to better understand the pharmacokinetics of mycophenolat mofetil during peritoneal dialysis.

Adult↗
PubMed1997

Endothelin-1 transgenic mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension.

The human endothelin-1 (ET-1) gene under the control of its natural promoter was transferred into the germline of mice. The transgene was expressed predominantly in the brain, lung, and kidney. Transgene expression was associated with a pathological phenotype manifested by signs such as age-dependent development of renal cysts, interstitial fibrosis of the kidneys, and glomerulosclerosis leading to a progressive decrease in glomerular filtration rate. This pathology developed in spite of only slightly elevated plasma and tissue ET-1 concentrations. Blood pressure was not affected even after the development of an impaired glomerular filtration rate. Therefore, these transgenic lines provide a new blood pressure-independent animal model of ET-1-induced renal pathology leading to renal fibrosis and fatal kidney disease.

Animals↗
PubMed1997

Maintenance therapy with triple versus double immunosuppressive regimen in renal transplantation: a meta-analysis.

BACKGROUND: The purpose of this study was to compare the effect of triple immunosuppressive maintenance therapy (cyclosporine, azathioprine, and prednisolone) with that of double therapy (cyclosporine and prednisolone) in renal transplant patients using graft failure, mortality, and acute rejection episodes as outcome measures. METHODS: A systematic overview of articles published between 1984 and 1995 was done. MEDLINE, Science Citation Index, reference lists, and expert files were searched. Of 449 originally identified studies, five controlled trials were finally selected. Information was retrieved on the topics of methodological quality, baseline characteristics, interventions, and outcomes. The Mantel-Haenszel fixed effect method was used to combine results from different studies. RESULTS: Pooled analysis did not show a statistically significant difference between triple-drug therapy and double-drug therapy in the main outcome of graft failure (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.61-1.16), survival (OR, 0.83; 95% CI, 0.57-1.21), or the occurrence of acute graft rejection (OR, 1.02; 95% CI, 0.76-1.36). There was a nonsignificant trend for better graft survival under triple therapy. A lower withdrawal rate suggests a more stable immunosuppressive effect on triple therapy. CONCLUSIONS: There is no statistically significant difference in the long-term management of renal transplant recipients between the two treatment regimens.

Acute Disease↗
PubMed1997

Interleukin-8 expression in patients after renal transplantation.

Cellular invasion and cytokine release are important steps in the initiation of rejection. We studied the release of interleukin-8 (IL-8), a potent proinflammatory and chemotactic cytokine, and its prognostic significance in predicting rejection after renal transplantation. Serum and urine samples were analyzed with an IL-8-specific sandwich enzyme-linked immunosorbent assay. Biopsy tissue specimens (n = 20) were snap-frozen and examined with immunohistochemistry using two monoclonal antibodies against human IL-8 (4G9 and 2A8). Serum IL-8 measurements were of no value in predicting rejection due to low sensitivity (24%). In 45 biopsy-proven acute rejections (< 2 months after transplantation), urinary IL-8 concentrations were elevated in 62% (298 +/- 54 pg/mL; P < 0.01), preceding clinical diagnosis of rejection. After treatment, the IL-8 concentration in urine decreased back to normal (33 +/- 4 pg/mL; P < 0.01). The highest urinary IL-8 concentrations were seen in patients with biopsy-proven rejection in combination with acute tubular necrosis (610 +/- 150 pg/mL). This finding was independent of renal function and urinary volume. Only three of 15 rejection episodes in patients more than 2 months after transplantation showed an elevated IL-8 concentration in urine (94 +/- 60 pg/mL). In 10 of 23 patients with infection, a significant increase of IL-8 in urine was observed as well (157 +/- 67 pg/mL; P < 0.05). IL-8-positive staining was found within interstitial mononuclear cells of all biopsy specimens showing rejection. Additionally, the antibody 4G9 stained arteriolar smooth muscle and tubular cells. Interestingly, a few IL-8-positive cells were present in two donor kidneys before transplantation was performed; control tissue was negative. Further investigations are necessary to determine the clinical value of urinary IL-8 determinations in the diagnosis of rejection and to evaluate the role of IL-8 in the pathogenesis of acute allograft rejection.

Enzyme-Linked Immunosorbent Assay↗
PubMed1997

The influence of age on outcome after renal transplantation.

The influence of donor age and recipient age on outcome after renal transplantation has been investigated in numerous studies. There is some evidence that patient survival in elderly patients who receive a transplant is significantly higher compared with those, who remain on dialysis. In general, patient survival after renal transplantation is mainly dependent on recipient age and on comorbid conditions. Concerning graft survival, most studies conclude that the survival of kidneys taken from older donors (> 50 years) and very young donors (< 5 years) is reduced. Graft survival was also found to be reduced in very young recipients (< 5 years). Functional graft survival proved to be better in older recipients (> 50 years) as compared to younger recipients, due to a reduced immunologic response capability. Actual graft survival however, where cases of death with functioning graft are included, is fairly equal in both populations. The question, whether the age difference between donor and recipient has an influence on graft survival, needs to be further investigated. In conclusion, donor and recipient age are important risk factors, which may influence outcome after renal transplantation and therefore should be considered carefully.

Age Factors↗
PubMed1997

Effects of early and late antihypertensive treatment on extracellular matrix proteins and mononuclear cells in uninephrectomized SHR.

The efficacy of an early and late treatment with the angiotensin converting enzyme inhibitor lisinopril or the angiotensin II receptor blocker ICI D8731 was investigated in uninephrectomized spontaneously hypertensive rats (SHR). Rats that underwent uninephrectomy (UNX) at six weeks of age were randomly assigned to receive no treatment, lisinopril shortly after UNX, lisinopril starting 16 weeks after UNX, ICI D8731 shortly after UNX, and ICI D8731 starting 16 weeks after UNX. Blood pressure was normalized with both treatments. After six months inulin clearance was not significant different, while proteinuria and prevalence of interstitial fibrosis were significantly reduced in all treatment groups. Immunohistochemical studies revealed an interstitial, periglomerular and perivascular increase of extracellular matrix proteins in all rats, but a markedly reduced expression of collagen I, IV and fibronectin after early and late treatment compared to untreated controls. We found a significant reduction of infiltrating macrophages and T-lymphocytes in all treated animals compared to untreated controls after 2, 4 and 6 months. Especially early treatment was associated with lower numbers of infiltrating cells. Both treatments reduced proliferation of tubular and interstitial cells. There were no striking differences with regard to nephroprotection between the ACE inhibitor and angiotensin II receptor blocker. These findings show that both treatments have beneficial effects on kidney structure and function. They suggest that both ACE inhibition and angiotensin II blockade decrease renal cell proliferation and suppress the infiltration of mononuclear cells that may trigger expression of extracellular matrix proteins and progressive nephrosclerosis.

Angiotensin Receptor Antagonists↗
PubMed1997

Glomerular epithelial cell products stimulate mesangial cell proliferation in culture.

Glomerular epithelial cells (GEC) and mesangial cells (MC) are both involved in glomerular diseases. To elucidate potential interactions between these glomerular cell types, we examined whether products of GEC affect the proliferative activity of MC. We found that cultured rat GEC secrete soluble factors into the supernate (GEC-CM) that induce proliferation of quiescent rat MC. The mitogenic activity was trypsin sensitive and partially heat-labile. Biochemical analysis of GEC-CM by gel filtration HPLC, reverse phase HPLC, and isoelectric focusing revealed at least three mitogenic fractions as well as inhibitory activity present in GEC-CM. Competitive binding assays with 125I-labeled PDGF did not show significant amounts of PDGF in GEC-CM. The biochemical features of the GEC-derived MC growth factors are distinct from IL-6, PDGF, bFGF, and endothelin, previously described GEC-derived MC growth factors. Additionally, significant contributions of known growth factors such as IL-1, IL-2, IL-3, IL-4, IL-5, TNF alpha, TGF beta, and GM-CSF are unlikely. The results indicate that GEC produce several biochemically-distinct MC growth regulators. While these epithelial cell-derived mitogens for MC require further characterization, they may play an important role in the regulation of MC replication, such as during embryogenesis and glomerular disease.

Animals↗
PubMed1997

Pharmacokinetics of temocapril and temocaprilat after 14 once daily oral doses of temocapril in hypertensive patients with varying degrees of renal impairment.

AIMS: The aim of this study was to determine the potential influence of renal impairment on the pharmacokinetics of temocapril and its pharmacologically active diacid metabolite, temocaprilat. METHODS: Non-compartmental pharmacokinetics were assessed in four groups of hypertensive patients (n=8 per group, four investigational centres) with normal (creatinine clearance determined via 24 h urine sampling, CL[CR], > or = 60 ml min-1) and impaired renal function (CL[CR] 40-59, 20-39, < 20 ml min-1) after 14 once daily oral doses of 10 mg temocapril hydrochloride. RESULTS: For temocapril, there were no statistically significant differences in median tmax or mean Cmax, AUC(SS), t1/2,Z, CL/F between the four groups. Renal clearance, CL(R), for temocapril showed a linear decreasing trend with decreasing CL(CR) [mean (s.d.): 32.2 (10.7) to 3.7 (3.0) ml min-1]. Steady-state for temocaprilat was reached on day 5. For temocaprilat, no statistically significant differences in mean Cmax or median tma were detected. With decreasing mean CL(CR), mean AUC(SS) for temocaprilat increased statistically significantly although only 2.4-fold [mean (s.d.): 2115 (565) to 4989 (2338) ng ml-1 h] and t1/2,Z was prolonged [mean (s.d.): 15.2 (1.2) to 20.0 (7.5) h]. CL(R) for temocaprilat showed a linear decreasing trend with decreasing CL(CR) [mean (s.d.): 20.2 (4.3) to 3.0 (1.8) ml min-1]. CONCLUSIONS: These results indicate that impaired renal function has only a limited effect on the pharmacokinetics of temocapril and its active metabolite, temocaprilat. This may be attributed to the dual, i.e. renal and biliary, elimination pathway of the drug.

Adult↗
PubMed1997

Interleukin-6 expression after renal transplantation.

BACKGROUND: Interleukin-6 (IL-6) is an inflammatory cytokine that plays a role in transplant rejection. We tested the hypothesis that IL-6 levels in serum or urine could be of value in predicting acute and chronic allograft rejection. Furthermore, we examined whether or not such levels reflected IL-6 expression in the kidney. METHODS: We measured IL-6 and IL-6 soluble receptor (IL-6sR) in serum and urine of 145 transplant patients and 20 normal controls. In parallel, we studied 108 renal biopsies. IL-6 was measured with a bioassay system using an IL-6 dependent cell line. IL-6sR was measured with enzyme-linked immunosorbent assay. The biopsies were examined for IL-6 and IL-6 receptor (IL-6R) expression with immunohistochemistry. RESULTS: Rejection episodes occurring within 2 months of transplantation were accompanied by elevated IL-6 concentrations in serum (17 +/- 4.8 pg/ml, P < 0.05) and urine (114 +/- 27 pg/ml, P < 0.005), compared to controls. These values returned towards baseline (0-5 pg/ml) after successful rejection treatment. The sensitivity of urine measurements was much higher (93%) than serum (54%). The specificity in serum (70%) and urine (60%) was reduced by infection, acute tubular necrosis, and antithymocyte globulin treatment. Serum and urine IL-6sR values did not correlate with rejection. In biopsy tissue, IL-6 and IL-6R were both elevated during rejection. Especially, mononuclear cells within the interstitial infiltrate stained positive. However, the amount of IL-6 positive cells did not correlate with peripheral IL-6 concentrations. CONCLUSIONS: Urine but not serum IL-6 values are sensitive indicators of rejection; however, they are confounded by infection, acute tubular necrosis, and certain antirejection treatments. These features limit their usefulness.

Acute Disease↗
PubMed1997

Blood pressure independent effects of nitrendipine on cardiac structure in patients after renal transplantation.

Left ventricular hypertrophy is well established as a blood pressure independent cardiovascular risk factor in patients on renal replacement therapy. The effects of antihypertensive treatment on myocardial structure and function in renal transplant recipients have been so far only rarely investigated. In a double-blind, placebo-controlled study patients were randomized to the calcium channel blocker nitrendipine or placebo if the transplanted kidney had developed a stable phase. Normotensive patients received nitrendipine 2 x 5 mg daily or placebo, hypertensive patients received 2 x 10 mg up to 2 x 20 mg nitrendipine daily or placebo. To achieve adequate blood pressure control, all patients with still elevated blood pressure on study medication received antihypertensive drugs other than calcium channels blockers. Ambulatory blood pressure recording and 2D-guided M-mode echocardiography were performed at baseline and upon completion of the study. In addition, laboratory workup (including serum creatinine and lipids) was done, and serum aldosterone, plasma renin activity, plasma angiotensin II and blood glucose levels were measured in all patients at baseline and after at least 12 months of therapy. Ambulatory blood pressure was almost identical between both groups at study baseline and follow-up. In renal transplant patients on nitrendipine, posterior wall thickness (-0.10 +/- 1.77 mm) and septal wall thickness (-0.83 +/- 2.23 mm) did not change significantly from baseline. In contrast, posterior wall thickness (0.71 +/- 0.92 mm, P < 0.01) and septal wall thickness (0.97 +/- 2.20 mm, P < 0.05) increased in patients on placebo, which differed from the observed changes on nitrendipine (ANOVA: P = 0.093 and P = 0.048, respectively). Relative wall thickness, a parameter for concentric left ventricular hypertrophy, became numerically smaller on nitrendipine therapy from 0.46 +/- 0.07 to 0.44 +/- 0.09 (-0.02 +/- 0.09, NS) but increased from 0.42 +/- 0.08 to 0.48 +/- 0.08 in the placebo arm (+0.04 +/- 0.08, P < 0.02), which was also significant between the two groups (ANOVA: P = 0.036). Endocrine parameters, lipids and blood glucose were not different between the two groups. We conclude from these data that the calcium channel blocker nitrendipine exerted beneficial effects on cardiac structure in patients after renal transplantation independent of blood pressure.

Adult↗
PubMed1997

The paracrine endothelin system: pathophysiology and implications in clinical medicine.

Apart from the initially described vasoconstriction, endothelins have been shown to cause a variety of biological activities in non-vascular tissues. A rapidly growing body of data supports the concept of endothelin as a paracrine acting hormone. In this review, we will discuss the impact of this local endothelin system for various cardiovascular pathophysiological states, especially atherosclerotic vascular disease, restenosis, myocardial infarction, congestive heart failure, and arterial hypertension. In addition, the endothelin system is a modulator of renal function via its binding to abundant receptors in renal tissue and by the ability of renal endothelial and epithelial cells to synthesize and release endothelin. In the kidney, endothelin may function as a paracrine/autocrine factor in the regulation of renal blood flow, glomerular haemodynamics, and sodium and water homeostasis. The renal endothelin system is involved in kidney diseases such as impaired renal function in liver cirrhosis, cyclosporin toxicity, acute renal failure and renal glomerular and interstitial fibrosis. Therapeutic approaches with new orally active endothelin receptor antagonists are also discussed.

Amino Acid Sequence↗
PubMed1997

Tc-99m DTPA perfusion scintigraphy and color coded duplex sonography in the evaluation of minimal renal allograft perfusion.

AIM: The clinical impact of perfusion scintigraphy versus color coded Duplex sonography was evaluated, with respect to their potential in assessing minimal allograft perfusion in vitally threatened kidney transplants, i.e. oligoanuric allografts suspected to have either severe rejection or thrombosis of the renal vein or artery. METHODS: From July 1990 to August 1994 the grafts of 15 out of a total of 315 patients were vitally threatened. Technetium-99m DTPA scintigraphy and color coded Duplex sonography were performed in all patients. For scintigraphic evaluation of transplant perfusion analog scans up to 60 min postinjection, and time-activity curves over the first 60 sec after injection of 370-440 MBq Tc-99m diethylenetriaminepentaacetate acid (DTPA) were used and classified by a perfusion score, the time between renal and iliac artery peaks (TDiff) and the washout of the renogram curve. Additionally, evaluation of excretion function and assessment of vascular or urinary leaks were performed. By color coded Duplex sonography the perfusion in all sections of the graft as well as the vascular anastomoses were examined and the maximal blood flow velocity (Vmax) and the resistive index (RI) in the renal artery were determined by means of the pulsed Doppler device. Pathologic-anatomical diagnosis was achieved by either biopsy or post-explant histology in all grafts. RESULTS: Scintigraphy and color coded Duplex sonography could reliably differentiate minimal (8/15) and not perfused (7/15) renal allografts. The results were confirmed either by angiography in digital subtraction technique (DSA) or the clinical follow up. CONCLUSION: In summary, perfusion scintigraphy and color coded Duplex sonography are comparable modalities to assess kidney graft perfusion. In clinical practice scintigraphy and color-coded Doppler sonography can replace digital subtraction angiography in the evaluation of minimal allograft perfusion.

Adult↗
PubMed1996

Paracrine renal endothelin system in rats with liver cirrhosis.

1. Liver cirrhosis was induced in rats by CCl4 administration. We analysed the expression of endothelin receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma as well as renal-tissue endothelin-1 concentrations using a specific radioimmunoassay. Furthermore, we analysed the effects of the non-selective (A/B) endothelin receptor antagonist, bosentan (6 and 100 mg kg-1 day-1) on mean arterial blood pressure, water and sodium excretion and glomerular filtration rate. 2. Our study revealed an overexpression of the endothelin B receptor (ETB) in the renal medulla of rats with liver cirrhosis (Cir: 2775 +/- 299 fmol mg-1; Con: 1695 +/- 255 fmol mg-1; n = 8; means +/- s.d., P < 0.01), whereas the density of ETB in the cortex and the endothelin A receptor (ETA) in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. 3. The tissue endothelin-1 concentrations were increased in the renal medulla of cirrhotic rats (Cir: 271 +/- 68 pg g-1wet wt.; Con: 153 +/- 36 pg g-1 wet wt., n = 8; means +/- s.d., P < 0.01). 4. The glomerular filtration rate was slightly decreased in cirrhotic rats but not altered after bosentan treatment in either cirrhotic or control rats. Bosentan decreased sodium excretion to a similar extent in both cirrhotic and control rats, whereas water excretion was significantly reduced by both dosages of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 +/- 0.62 m day-1, Cir + 6 mg kg-1 day-1 bosentan: 8.6 +/- 1.0 ml day-1; Cir + 100 mg kg-1 day-1 bosentan: 7.4 +/- 0.6 ml day-1; n = 10; means +/- s.e.mean). 5. We therefore suggest that the upregulation of the medullary ETB in cirrhotic rats is involved in the regulation of water excretion in rats with CCl4-induced liver cirrhosis.

Animals↗