Influence of antihypertensive treatment with budralazine on autoregulation of cerebral blood flow in spontaneously hypertensive rats.
We studied the effect of chronic antihypertensive treatment with budralazine on the lower blood pressure limit of cerebral blood flow autoregulation using spontaneously hypertensive rats. Cerebral blood flow in the parietal cortex and caudate nucleus was measured to determine the lower limit using the hydrogen clearance method. The lower limit in both cerebral regions was significantly higher in 10 untreated spontaneously hypertensive rats than in 10 Wistar-Kyoto rats. The upward-shifted lower limit was restored to close to normal in the caudate nucleus and was partially restored in the parietal cortex of nine rats by 9 weeks of treatment with the high dose (50-68 mg/kg/day) of budralazine, which kept blood pressure constant at approximately normotension during the treatment period; the lower limit was slightly restored in both cerebral regions of seven rats by 4 weeks of treatment with the high dose. However, 9 weeks of treatment with the low dose (19-27 mg/kg/day) of budralazine, which produced moderate continuous hypotension in nine rats, did not apparently influence the lower limit. Our results suggest that long-term antihypertensive therapy with budralazine reduces the upward-shifted lower blood pressure limit of cerebral blood flow autoregulation toward normal and that the restoration induced by budralazine depends on the degree of blood pressure reduction as well as on the duration of the therapeutic period.
Tanaka
S
S
Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Tanaka
M
M
Akashi
A
A
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D006830:Hydralazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY; D012016:Reference Values
D000959:Antihypertensive Agents; D006830:Hydralazine; C006153:budralazine