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      Prepubertal Treatment with Angiotensin Receptor Blocker Causes Partial Attenuation of Hypertension and Renal Damage in Adult Dahl Salt-Sensitive Rats

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          Recently, we have shown that treatment of stroke-prone spontaneously hypertensive rats with angiotensin inhibitors for a limited time-window before puberty results in an attenuation of hypertensive nephrosclerosis in later life. The aim of this study was to examine the applicability of this therapeutic paradigm to a low-renin model. Dahl salt-sensitive (Dahl-S) rats were fed a high-salt diet from age 6 weeks. Some rats were treated with the angiotensin receptor blocker (ARB) candesartan cilexetil (2 mg/kg/d) from weaning to puberty (age 3–10 weeks), whereas other rats were treated continuously until overt renal damage was seen (age 3–16 weeks). Dahl-S rats on a high salt diet had increased blood pressure (207 ± 3 vs. 125 ± 2 mm Hg), proteinuria, and glomerular/vascular histological changes. The prepubertal treatment with ARB resulted in a continued suppression of blood pressure (153 ± 2 mm Hg) at 16 weeks. Both proteinuria and renal histological changes were significantly (p < 0.05) attenuated, but not completely prevented by the treatment. No significant differences in plasma renin activity, renin mRNA, or AT1/AT2 mRNA were seen between groups. These results suggest that prepubertal treatment affords sustained renoprotection, even in an animal model with a suppressed renin-angiotensin system, and support the notion that appropriate prepubertal intervention may lead to a partial attenuation in the susceptibility to inherited renal diseases.

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          The debate on the ‘amplifier hypothesis’ - some comments

           Björn Folkow (2000)

            Author and article information

            S. Karger AG
            August 2002
            15 July 2002
            : 91
            : 4
            : 710-718
            Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
            65035 Nephron 2002;91:710–718
            © 2002 S. Karger AG, Basel

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            Figures: 6, Tables: 1, References: 21, Pages: 9
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