Amiloride reduces stroke and renalinjury in stroke-prone hypertensive rats.
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% NaCl 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.
Sepehrdad
Reza
R
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Chander
Praveen N
PN
Oruene
Alafuro
A
Rosenfeld
Louis
L
Levine
Seymour
S
Stier
Charles T
CT
D000584:Amiloride / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000473:pathology; D004232:Diuretics / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000235:genetics* / Q000473:pathology / Q000652:urine; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000235:genetics* / Q000517:prevention & control*; D016019:Survival Analysis
D004232:Diuretics; D000584:Amiloride