IngentaConnect Renal haemodynamics and function in weanling rats treated with en...

Abstract:

SUMMARY

1. Inhibition of the renin–angiotensin system (RAS) during kidney development produces chronic alterations in renal morphology and function that have been characterized in detail in adult animals. The aim of the present study was to determine the consequences of neonatal angiotensin-converting enzyme (ACE) inhibition on renal haemodynamics and function in rats at a much earlier age, namely 3–4 weeks.

2. Male Wistar pups received daily intraperitoneal injections of enalapril (10 mg/kg) or isotonic saline from birth until 24–28 days of age, when renal haemodynamics and function were assessed using clearance techniques under pentobarbital anaesthesia.

3. Enalapril-treated rats showed significant reductions in glomerular filtration rate (GFR; -44 ± 6%; P < 0.05), effective renal plasma flow (ERPF; -33 ± 6%; P < 0.05) and filtration fraction (-16 ± 3%; P < 0.05) compared with saline-treated controls. Although mean arterial pressure tended to be lower in enalapril-treated rats, this group demonstrated a significant increase in renal vascular resistance compared with control rats (RVR; 46 ± 6 vs 32 ± 3 mmHg/mL per·min per g·kidney weight, respectively; P < 0.05). In enalapril-treated rats, urine osmolality was reduced (-59 ± 5%; P < 0.05) and urine flow rate and fractional urinary excretion rates of sodium and potassium were markedly elevated compared with controls (P < 0.05). Enalapril-treated rats showed severe renal histological abnormalities, including wall thickening of cortical arterioles, papillary atrophy and tubulointerstitial alterations, mimicking those described previously in similarly treated rats examined in adulthood.

4. In conclusion, neonatal ACE inhibition in rats induces pronounced alterations in renal haemodynamics and function, characterized by reductions in ERPF and GFR, increased RVR and impaired tubular sodium and water reabsorption, which are evident at weaning.

Keywords: angiotensin-converting enzyme inhibitor; kidney development; kidney function; renin–angiotensin system

Document Type: Original article

DOI: 10.1111/j.1440-1681.2010.04278.x

Affiliations: 1: Department of Nephrology, Institute of Internal Medicine and Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden

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Renal haemodynamics and function in weanling rats treated with enalapril from birth