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- Title
Amiloride reduces stroke and renalinjury in stroke-prone hypertensive rats
- Authors
Sepehrdad, Reza; Chander, Praveen N.; Oruene, Alafuro; Rosenfeld, Louis; Levine, Seymour; Stier Jr, Charles T.
- Abstract
: BackgroundWe 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.: MethodsIn 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% NaCl drinking solution. Systolic BP, proteinuria, body weight, and renal and brain histopathology were assessed.: ResultsAcute 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.: ConclusionsThese 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.
- Subjects
PROTEINURIA; BLOOD pressure
- Publication
American Journal of Hypertension, 2003, Vol 16, Issue 4, p312
- ISSN
0895-7061
- Publication type
Article
- DOI
10.1016/S0895-7061(03)00006-2