Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats

Stroke-prone spontaneously hypertensive rats (SHRSP). subjected to high NaC l, show severe hypertension, organ damage, and early death. Preventive trea tment with angiotensin II type 1 (AT,) receptor antagonists is known to be effective. Previously, we found that angiotensin converting enzyme (ACE) in hibition could reduce cerebral edema when treatment was started after manif estation of either proteinuria or cerebral edema. In this study AT, recepto r blockade was started at the same time points to evaluate whether this had an effect superior to ACE inhibition. SHRSP drank 1% NaCl. Group I served as controls. Group 2 and 3 rats were started on losartan and enalapril afte r proteinuria exceeded 40 mg/day. Group 4 and 5 rats were started on losart an and enalapril after the first observation of cerebral edema with T2-weig hted magnetic resonance imaging scans. In controls, median survival was 54 days (range, 35 to 80 days) after the start of salt loading. With early-ons et losartan and enalapril, survival increased to 305 days (range, 184 to 42 2 days) and 320 days (range, 134 to 368 days) (both P < .01 v group 1). Cer ebral edema formation was prevented in all but two rats, one from each trea tment modality. Development of proteinuria was markedly reduced. With late- onset treatment with losartan and enalapril, survival was 290 days (range, 120 to 367 days) and 264 days (range, 154 to 319 days) (both P < .01). Both losartan and enalapril decreased cerebral edema to baseline levels. Ultima tely cerebral edema reoccurred, despite continued treatment, in 75% of the rats. Systolic blood pressure did not decrease after losartan treatment, bu t, similarly to early-onset treatment, decreased transiently after enalapri l treatment. Cerebral edema and proteinuria were prevented and reduced in S HRSP treated with either an AT, receptor antagonist or an ACE inhibitor. Su rvival was markedly and similarly prolonged by both treatments, whether ini tiated directly before or after development of cerebral edema. In rats wher e treatment was initiated after manifestation of cerebral edema, both cereb ral edema and proteinuria reappeared despite continued treatment. Apparentl y, when hypertension is sustained, reappearance of target organ damage may not be entirely dependent on angiotensin. (C) 2001 American Journal of Hype rtension, Ltd.