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

We recently reported that spironolactone and eplerenone, mineralocorticoid receptor (MR) antagonists, markedly reduced proteinuria and vascular injury in saline-drinking stroke-prone spontaneously hypertensive rats (SHRSP). Presently, we examined whether amiloride (AMIL), a highly effective sodium channel blocker, would mimic the effect of MR antagonists against the development of pathology in these rats. Saline-drinking SHRSP were either untreated (control, n=7) or given AMIL (1 mg/Kg/day in the drinking solution, n=8) starting at 8.5 weeks of age. Six of seven control SHRSP showed signs of stroke with 71 % mortality at 13 weeks of age. All of the eight AMIL-treated SHRSP continued to gain body weight and showed no signs of stroke through 14.6 weeks of age. Urinary protein excretion was 101 ± 23 v 18 ± 1 mg/day, respectively, in the control and AMIL groups (P<0.002) at 11.6 weeks of age. Systolic blood pressure was 228±6 and 217±3 mmHg, respectively, in the control and AMIL groups at this time (P>0.1). Hematocrit was significantly lowered in control (45.7 ± 1.5 %) v AMIL-treated (53.5 ± 0.8 %) SHRSP (P<0.002) which is consistent with the development of thrombotic microangiopathic injury in the former group. The urinary sodium to potassium concentration ratio averaged 4.7 in these saline-drinking animals and was not increased by AMIL treatment. These findings implicate a role for sodium channels in the evolution of vascular injury in saline-drinking SHRSP. Whether this involves a renal or extrarenal effect requires further investigation.