Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria in subtotally nephrectomized rats

A potential role of the sympathetic nervous system in progression of renal failure has received little attention. This study examined whether nonhypot ensive doses of moxonidine, an agent that reduces sympathetic activity, aff ects glomerulosclerosis, urine albumin excretion, and indices of renal hand ling of norepinephrine (NE) in subtotally nephrectomized (SNX) rats. Spragu e Dawley rats were SNX or sham-operated (control). SNX rats were either lef t 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, and in situ hybridization, Urine albumin excretion rate was analyzed by enz yme-linked immunosorbent assay, and kidney angiotensin LI and NE content we re measured using HPLC,H-3-NE uptake, and release. Body and kidney weight a nd BP were not significantly different between SNX with or without moxonidi ne. The glomerulosclerosis index was significantly lower in moxonidine-trea ted (0.88 +/- 0.09) compared with untreated (1.55 +/- 0.28) SNX rats, as wa s the index of vascular damage (0.32 +/- 0.14 versus 0.67 +/- 0.16). The nu mber of proliferating cell nuclear antigen positive glomerular and tubular cells per area was significantly higher in untreated SNX rats than in contr ols and moxonidine-treated SNX rats. The same was true for urine albumin ex cretion rate. Renal angiotensin LT tissue concentration was not affected by moxonidine. In untreated SNX rats, renal nerve stimulation and exogenous N E induced an increase in isolated kidney perfusion pressure (102 +/- 21 ver sus 63 +/- 8 mmHg). Renal endogenous NE content was significantly lower in SNX rats than in controls (86 +/- 14 versus 140 +/- 17 pg/mg wet weight). C ortical uptake of [H-3]-NE was not different, but cortical NE release was s ignificantly higher in SNX rats than in controls. Reduced function of presy naptic inhibitory cu-adrenoreceptors is unlikely because an alpha(2)-adreno ceptor antagonist increased NE release. At subantihypertensive doses, moxon idine ameliorates renal structural and functional damage in SNX animals, po ssibly 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.