Effect of chronic treatment with angiotensin receptor ligands on water-salt balance in wistar and spontaneously hypertensive rats

Abstract

The renin-angiotensin system plays a crucial role in the regulation of cardiovascular function and maintenance of water-electrolyte balance. The two major receptor types of the system, AT1 and AT2, have different, often opposite effects on these functions. To elucidate the impact of long-term treatment with selective angiotensin receptor antagonists and an agonist on water-salt balance in normotensive Wistar and spontaneously hypertensive rats (SHRs). 12-week-old male Wistar rats and SHRs were individually housed in metabolic cages and 24-h food and water intake and urine and electrolyte excretion were measured. Urinary sodium (UNa), potassium (UK) and chlorine (UCl) were determined by a flame photometer. Losartan, a selective AT1 receptor antagonist, was administered in the Wistar rats and SHRs at a dose of 10 mg/kg/day subcutaneously (sc). Wistar rats were also given the AT2 receptor antagonist, PD123319, subcutaneously at a dose of 10 mg/kg/ day. CGP 42112A, an AT2 receptor agonist, was administered intracerebroventricularly in Wistar rats at a dose of 12 microg/rat/day. The drugs were infused continuously for 14 days through osmotic minipumps. Losartan selectively increased sodium excretion in both rat strains and decreased weight gain in SHRs. PD123319 increased potassium excretion and decreased weight gain in Wistar rats. CGP 42112A increased food and water intake, urine output and UNa+ and UK+ excretion and decreased weight gain in normotensive Wistar rats. Chronic treatment with selective angiotensin receptor ligands modifies water-salt balance in rats through changes both in renal excretory function and ingestive behaviors.