Author:
AMANN KERSTIN,RUMP LARS CHRISTIAN,SIMONAVICIENE AURELIA,OBERHAUSER VITUS,WESSELS SABINE,ORTH STEPHAN R.,GROSS MARIE-LUISE,KOCH ANDREAS,BIELENBERG GERHARD W.,VAN KATS JORGE P.,EHMKE HEIMO,MALL GERHARD,RITZ EBERHARD
Abstract
Abstract.A potential role of the sympathetic nervous system in progression of renal failure has received little attention. This study examined whether nonhypotensive doses of moxonidine, an agent that reduces sympathetic activity, affects glomerulosclerosis, urine albumin excretion, and indices of renal handling of norepinephrine (NE) in subtotally nephrectomized (SNX) rats. Sprague Dawley rats were SNX or sham-operated (control). SNX rats were either left untreated or treated with moxonidine in a dose (1.5 mg/kg body wt per d) that did not modify telemetrically monitored 24-h BP. Glomerular and renal morphology were evaluated by quantitative histology, immunohistochemistry, andin situhybridization. Urine albumin excretion rate was analyzed by enzyme-linked immunosorbent assay, and kidney angiotensin II and NE content were measured using HPLC,3H-NE uptake, and release. Body and kidney weight and BP were not significantly different between SNX with or without moxonidine. The glomerulosclerosis index was significantly lower in moxonidine-treated (0.88 ± 0.09) compared with untreated (1.55 ± 0.28) SNX rats, as was the index of vascular damage (0.32 ± 0.14versus0.67 ± 0.16). The number of proliferating cell nuclear antigen-positive glomerular and tubular cells per area was significantly higher in untreated SNX rats than in controls and moxonidine-treated SNX rats. The same was true for urine albumin excretion rate. Renal angiotensin II tissue concentration was not affected by moxonidine. In untreated SNX rats, renal nerve stimulation and exogenous NE induced an increase in isolated kidney perfusion pressure (102 ± 21versus63 ± 8 mmHg). Renal endogenous NE content was significantly lower in SNX rats than in controls (86 ± 14versus140 ± 17 pg/mg wet weight). Cortical uptake of [3H]-NE was not different, but cortical NE release was significantly higher in SNX rats than in controls. Reduced function of presynaptic inhibitory α-adreno-receptors is unlikely because an α2-adrenoceptor antagonist increased NE release. At subantihypertensive doses, moxonidine ameliorates renal structural and functional damage in SNX animals, possibly through central inhibition of efferent sympathetic nerve traffic. In kidneys of SNX rats, indirect evidence was found for increased activity of a reduced number of nerve fibers.
Publisher
American Society of Nephrology (ASN)
Subject
Nephrology,General Medicine
Cited by
172 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献