Amiloride reduces stroke and renal injury in stroke-prone hypertensive rats

Abstract

Background : We previously reported that the mineralocorticoid receptor antagonists spironolactone and eplerenone markedly reduce proteinuria and vascular injury in saline-drinking stroke-prone spontaneously hypertensive rats (SHRSP). Presently, we examined whether amiloride, an epithelial sodium channel blocker, would also protect against pathology in these rats. Methods: In acute studies, saline-drinking SHRSP (n = 5) were instrumented with radiotelemetry blood pressure (BP) probes and housed in metabolic cages. Mean arterial pressure and electrolyte excretion were quantified over the 24-h period after oral administration of vehicle or amiloride at 1, 3, 10, and 30 mg/kg. In a survival study, 8.5-week-old SHRSP were either untreated (control, n = 7) or given amiloride ( 1 mg/kg/day, n = 8) in their 1% NaCI drinking solution. Systolic BP, proteinuria, body weight, and renal and brain histopathology were assessed. Results: Acute amiloride treatment did not alter urine output, urinary electrolyte excretion, and sodium-to-potassium ratio or body weight. The mean arterial pressure was unaffected except for a 16-mm Hg reduction at 30 mg/kg (P <.01). Six of eight SHRSP chronically treated with amiloride survived through 20 weeks of age, whereas all control SHRSP died by 16.4 weeks (P <.0001). Amiloride delayed proteinuria (119 ± 24 v 15 ± 2 mg/day, P < .002) with no significant effect on systolic BP (228 ± 6 v 217 ± 4 mm Hg) at 12 weeks of age. Conclusions: These findings suggest that interference with sodium channel function, perhaps at sites other than the kidney epithelium, may play a role in protecting against the evolution of cerebral and renal vascular injury in saline-drinking SHRSP.