Role of growth hormone in the development of experimental renal scarring.

Recent experimental data has implicated growth hormone in the development of glomerular sclerosis. In this study, we have examined the development and progression of glomerular and tubulointerstitial scarring in Wistar and Dwarf rats, selectively growth hormone-deficient, following subtotal nephrectomy. Wistar rats showed progressive proteinuria, hypertension and renal failure as well as severe renal scarring 120 days after subtotal nephrectomy. In contrast, growth hormone-deficient Dwarf rats had minimal proteinuria, mild renal functional impairment and moderate renal histological scarring. The difference in these functional and structural parameters between the two strains is highly significant, although both experimental groups had comparable food consumption and systemic blood pressure. The significantly smaller glomeruli and limited kidney hypertrophy over 120 days observed in Dwarf rats may account for some of the protection against glomerular sclerosis and tubulointerstitial scarring observed in that strain.

Effect of antihypertensive therapy in experimental chronic renal failure.

In this study, the effect of the antihypertensive agents nifedipine (4.5 mg/day) and hydralazine (50-200 mg/l of drinking water) on the progression of chronic renal failure and scarring was evaluated in rats submitted to subtotal (5/6) nephrectomy (SNx). The effect of blood pressure reduction was studied in groups of rats fed either a medium-protein diet (24%) or high-protein diet (50%). SNx rats fed a high-protein diet had significantly higher levels of proteinuria and severer renal scarring at sacrifice (120 days after SNx). Nifedipine reduced proteinuria in SNx rats fed a high-protein diet. Both drugs significantly reduced systemic hypertension in SNx rats. Hydralazine and nifedipine also reduced hypertriglyceridaemia but had no effect on blood cholesterol levels. However, in spite of adequate control of systemic hypertension with the agents studied, the severity of renal scarring (glomerular sclerosis or tubulo-interstitial scarring) was not affected by treatment. We confirm that the control of systemic hypertension is not sufficient to prevent renal scarring in rats submitted to extensive renal ablation.

Effect of treatment with enalapril, verapamil and indomethacin on compensatory renal growth in the rat.

Renal growth often precedes scarring in experimental models of chronic renal failure in rats. Its control may therefore influence the subsequent development of renal scarring and failure in these animals. In this study we have attempted to manipulate, by pharmacological interventions, compensatory renal growth in rats who have undergone uninephrectomy. The effects of three drugs--enalapril, verapamil and indomethacin--were investigated. Compensatory renal growth was found to be 15.33 +/- 13.76% (mean +/- SD) 1 week after uninephrectomy in control adult male Wistar rats. Compensatory renal growth was significantly inhibited by pretreatment with enalapril 7.38 +/- 8.88% (P less than 0.05) but was unaffected by indomethacin; the effect of verapamil was inconclusive. In controls, both the protein and DNA content of the remaining kidney increased, indicating a mixed hypertrophic and hyperplastic response. Enalapril inhibited the hyperplastic component of compensatory renal growth. We conclude that following uninephrectomy in rats, compensatory hypertrophy can be manipulated by pharmacological interventions, in particular angiotensin-converting-enzyme inhibition by enalapril.

Compensatory renal growth: role of growth hormone and insulin-like growth factor-I.

Recent experimental evidence suggests that insulin-like growth factor-I (IGF-I) may be involved in compensatory renal growth (CRG). This study was designed to determine the relative contribution of IGF-I and growth hormone (GH) to the CRG that takes place in rats following uninephrectomy (UNx). We also studied the respective role of GH and IGF-I in the stimulation of CRG induced by a high protein diet (HPD). CRG was studied 7 days after UNx in Wistar rats and in a new mutant strain of dwarf rats, selectively deficient in GH. Prior to UNx, rats of both strains were pre-fed (14 days) either a medium-protein diet (MPD, casein 18%) or a HPD (54%). On MPD, CRG was comparable in Wistar (17.6 +/- 3.1%, M +/- SD) and dwarf (14.4 +/- 4.8%) rats. The HPD enhanced CRG in the Wistars (27 +/- 3.9%, P less than 0.005) but not in the dwarfs (14.9 +/- 2%). CRG in both experimental groups involved renal hypertrophy and hyperplasia. Control (baseline) serum, liver and kidney IGF-I were significantly less in dwarf rats. However, following UNx, on a MPD, kidney IGF-I increased significantly in both Wistar and dwarf rats: Wistar, pre-UNx, 310 +/- 46 ng/g tissue; post-UNx, 405 +/- 54 ng/g, P less than 0.005; dwarfs, pre-UNx, 205 +/- 35 ng/g; post-UNx 426 +/- 90 ng/g, P less than 0.001. On a HPD a further significant increase in renal IGF-I was only observed in Wistar rats (505 +/- 46 ng/g). No change in serum or liver IGF-I was observed after UNx in either strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary protein and insulin-like growth factor-I content following unilateral nephrectomy.

The compensatory renal growth (CRG) that follows unilateral nephrectomy (UNx) in the rat is blunted by a low protein diet (LPD). CRG in rats is associated with a parallel increase in insulin-like growth factor (IGF)-I/somatomedin-C content of the kidney. In this study, we have examined the effects of dietary protein manipulations on IGF-I and -II within remaining kidneys of rats during CRG following UNx. Adult Wistar rats were given a LPD (8% wt/wt casein), medium protein diet (MPD, 18%), or high protein diet (HPD, 78%) for 30 days prior to surgery. At surgery, either a right UNx or a sham operation was performed. Four days later, animals were sacrificed. Kidney weight, protein, DNA, IGF-I and -II contents were measured. Serum and hepatic content of IGF-I were also measured. CRG (%) was calculated comparing kidney weights pre- and post-UNx and between UNx and sham operated rats at sacrifice. At sacrifice, kidney weight was proportional to dietary protein intake in sham and UNx rats. Fractional kidney wt was significantly increased in UNx rats on each of the three diets compared to sham operated animals (P less than 0.001), but was greater in rats on HPD (35%) compared to those on MPD (23%) or LPD (20%). CRG was minimal on LPD (9.6 +/- 6.8%), compared to MPD (23.8 +/- 9.6%) and HPD (43.8 +/- 25.4%). The mean kidney content of IGF-I did not differ between dietary groups in sham operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)