Acetazolamide and enalapril combination offers complete protection from nitric oxide-deficient stroke in stroke-prone spontaneously hypertensive rats.

Chronic oral administration of l -NAME precipitates stroke in stroke-prone spontaneously hypertensive rats (SHRSP). The present study investigated whether acetazolamide (an acidotic agent) given alone or in combination with an angiotensin blocker (enalapril maleate) offers any protection from NO-deficient stroke in SHRSP. We also examined whether protection from NO-deficient stroke involves activation of K(+)channels. Five-week-old SHRSP drank saline (group I), l -NAME (group II), l -NAME+enalapril (group III), l -NAME+acetazolamide (group IV), and l -NAME+enalapril+acetazolamide (group V). Within a few hours following onset of stroke, rats were attached to a blood pressure recorder. In subsequent experiments, to investigate the involvement of K(+)channels, glibenclamide and BaCl(2)(K(+)channel blockers) were included in the drinking solutions that were given to the SHRSP groups receiving l -NAME, acetazolamide and enalapril. Group I of SHRSP did not develop stroke. Group II, III and IV developed stroke in 12+/-2, 29+/-2 and 20+/-2 days, respectively. SHRSP from group V did not develop stroke. However, they died in 70+/-2 days. The glibenclamide and BaCl(2)administration failed to prevent this protection from stroke. In conclusion, concurrent administration of acetazolamide and enalapril prevents onset of NO-deficient stroke in SHRSP. These stroke-protective effects are independent of reductions in mean or systolic blood pressures and do not involve an activation of K(+)channels. Copyright 2000 Academic Press.