Preservation of Renal Function in the Rat Remnant Kidney Model of Chronic Renal Failure by Blood Pressure Reduction

Jackson, Bruce; Debrevi, L.; Cubela, Rose; Whitty, M.; Johnston, Colin I.

doi:10.1111/j.1440-1681.1986.tb00356.x

Cited by 25 publications

(16 citation statements)

References 7 publications

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“…These effects on the remnant kidney function in this model of rats following blood pressure reduction by calcium channel blockers are consistent with the previous reports (Jackson et al 1986; Jackson and Johnston 1988). Treatment of hypertension with indapamide, possessing both natriuretic and direct vasodilatory activity (Van Zwieten 1984), or the calcium channel blocker benidipine, produced a milder and comparable decrease in blood pressure, but had dissimilar effects on renal function in SHR with reduced renal mass.…”

Section: Discussionsupporting

confidence: 81%

Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation.

Yasujima

Abe

Kanazawa

et al. 1989

Tohoku J. Exp. Med.

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Section: Discussionsupporting

confidence: 81%

Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation.

Yasujima

Abe

Kanazawa

et al. 1989

Tohoku J. Exp. Med.

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“…Eliahou et al [15] administered nisoldipine starting immediately after renal ablation, which prevented hypertension, had little effect on proteinuria, but improved survival in male and female Charles River rats. These reports of beneficial effects of calcium antagonists are at variance with studies in remnant-kidney rats performed earlier in our laboratory [1] and by Jackson et al [13]. The latter authors reported a tendency to increased proteinuria in female Sprague-Dawley rats despite excellent control of hypertension after 6 weeks of treatment with the calcium channel blocker felodipine.…”

Section: Introductioncontrasting

confidence: 56%

“…However, in the most extensively studied model of chronic renal failure, the remnantkidney rat, the response to different antihypertensive regimens is not uniform. Control of hypertension by ACE inhibitors has proven to be superior to triple-drug therapy with hydralazine, reserpine, and hydrochlorothiazide regarding prevention or delay in progressive glomerulosclerosis [12], and the highly protective effect of ACE inhibitors was invariably associated with greatly reduced proteinuria [1,12,13].…”

Section: Introductionmentioning

confidence: 99%

Control of Hypertension by Yerapamil Enhances Renal Damage in a Rat Remnant Kidney Model

Brunner

Bock

Hermle

et al. 1991

Nephrology Dialysis Transplantation

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Abstract. The effect of calcium channel blockers on the progression of renal failure is controversial. In contrast with earlier studies, we recently reported that moderately large doses of verapamil significantly accelerated chronic renal failure in the rat remnant kidney model [1]. Studies reporting beneficial effects of verapamil were characterised by a much lower dose of verapamil and by the start of treatment immediately after renal ablation, which potentially interfered with the initial phase of remnant kidney hypertrophy. We therefore studied the effects of a high, fully antihypertensive oral dose of verapamil (100-150 mg/kg/per day; group Vera high) and a low, haemodynamically almost ineffective dose (10-15 mg/kg per day; group Vera low), on the progression of chronic renal failure in female Wistar rats with 5/6 nephrectomy. The treatment was started no earlier than 5 weeks after renal ablation, and matched groups of 20 animals were followed for 16 weeks thereafter. High-dose verapamil reduced systolic blood pressure to median values of 130-140 mmHg throughout the experimental period, whereas blood pressure in Vera low animals remained elevated at median values of 165-172 mmHg similar to non-treated rats with 172-185 mmHg median systolic blood pressure.Despite control of hypertension, proteinuria increased more rapidly and to more elevated values in the Vera high animals (5.98 ± 0.91 mg/jumol creatinine before death/sacrifice) than in the Vera low and control groups (3.08 ± 0.91 and 3.60 ± 0.71 mg//imol creatinine, respectively, P < 0.05 vs Vera high), and signifiCorrespondence and offprint requests to: Professor F. P. Brunner, Kantonsspital Basel, 4031 Basel, Switzerland. cantly more animals died during the observation period in the Vera high compared to the control group (6 of 20 vs lof 20, P < 0.05). Kidney remnants were larger in the Vera high group, mainly due to tubulointerstitial changes with filling of dilated tubular lumina with proteinaceous casts. Mean glomerular diameter did not differ between groups, and the percentage of glomeruli with segmental or global glomerulosclerosis was not significantly increased in the Vera high group.It is concluded that chronic high-dose verapamil therapy in the 5/6 nephrectomy model, albeit effective in controlling hypertension, is deleterious to renal function when remnant hypertrophy has previously been allowed to occur. A low, haemodynamically barely effective, dose of verapamil fails to alter the course of renal failure in this setting.

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“…These results can be ascribed, to a great extent, to the lower SBP observed in MNF rats up to 6 wk of observation ( Table 1). The importance of reducing blood pressure to slow the progression of CRF, in fact, is widely recognized in many experimental and clinical studies, with the best results obtained with angiotensin-converting enzyme inhibitors, which increase the availability of NO (13,14,17,20). All of these studies have clearly demonstrated the direct correlation between the levels of SBP and both the functional and histological damage in the kidney; this study further strengthens how lower levels of SBP may positively influence the course of CRF, mostly when associated to a greater availability of NO, as in the case of MNF rats.…”

Section: Discussionmentioning

confidence: 99%

Arginase inhibition slows the progression of renal failure in rats with renal ablation

Sabbatini¹,

Pisani²,

Uccello³

et al. 2003

American Journal of Physiology-Renal Physiology

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nase inhibition slows the progression of renal failure in rats with renal ablation. Am J Physiol Renal Physiol 284: F680-F687, 2003. First published December 10, 2002 10.1152/ajprenal.00270.2002. Exogenous arginine slows the progression of chronic renal failure (CRF) in remnant rats through a nitric oxide (NO)-dependent mechanism. We tested whether the inhibition of arginase could induce similar results through the increased availability of endogenous arginine. Three groups of remnant rats were studied for 8 wk: 1) untreated rats (REM); 2) remnant rats treated with 1% L-arginine (ARG); and 3) remnant rats administered a Mn 2ϩ -free diet to inhibit arginase (MNF). Normal rats (NOR) were used as controls. Liver arginase activity was depressed in MNF rats (Ϫ35% vs. REM, P Ͻ 0.01). No difference in metabolic data was detected among the groups throughout the study; blood pressure was significantly lower in MNF vs. ARG and REM rats after 6 wk (P Ͻ 0.001). The glomerular filtration rate (GFR) was greatly depressed in REM rats (Ϫ47% vs. NOR, P Ͻ 0.03) but was higher in ARG and MNF rats (ϩ40 and ϩ43% vs. REM, respectively, P Ͻ 0.05), with comparable changes in renal hemodynamics. Despite the better GFR, proteinuria was decreased in both ARG and MNF rats (Ϫ42%, P Ͻ 0.05, and Ϫ57%, P Ͻ 0.01, respectively, vs. REM rats). Arginine plasma levels, significantly reduced in REM rats (Ϫ41% vs. NOR, P Ͻ 0.01), were partially restored in MNF rats (ϩ38% vs. REM), and urinary nitrite excretion, greatly depressed in REM rats (Ϫ76% vs. NOR, P Ͻ 0.01), was significantly increased in MNF rats (ϩ209% vs. REM, P Ͻ 0.05). At the renal level, arginase activity was only slightly depressed in MNF rats (Ϫ18% vs. REM), but intrarenal concentrations of arginine were lower in this latter group (P Ͻ 0.05 vs. other groups). Beyond the hemodynamic modifications, MNF rats showed a lower glomerular sclerosis index (P Ͻ 0.05 vs. REM and ARG). Inhibition of arginase slows the progression of CRF in remnant rats similarly to argininetreated rats; the better histological protection in MNF rats, however, suggests that additional factors are involved in these modifications. remnant rat; arginine; nitric oxide; chronic renal failure THE METABOLISM OF ARGININE is particularly complex: this semiessential amino acid, in fact, is endogenously synthesized in renal proximal tubules from L-citrulline (Citr) and is then degraded, through distinct enzymatic routes, to several metabolites that may affect both renal function and morphology (25,38). The first important pathway is represented by arginase, mostly present in the liver and to a much lesser extent in the kidney, which leads to formation of urea and ornithine (Orn), the precursor of polyamines and proline involved in cell-replication turnover and collagen synthesis (25). The second metabolic route is constituted by the arginine decarboxilase (ADC

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Preservation of Renal Function in the Rat Remnant Kidney Model of Chronic Renal Failure by Blood Pressure Reduction

Cited by 25 publications

References 7 publications

Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation.

Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation.

Control of Hypertension by Yerapamil Enhances Renal Damage in a Rat Remnant Kidney Model

Arginase inhibition slows the progression of renal failure in rats with renal ablation

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