Effect of an antihypertensive drug on brain angiotensin II levels in renal and spontaneously hypertensive rats.
1. Although numerous studies suggest that brain angiotensin (AII) may play an important role in the regulation of blood pressure, it is still unclear what factors may influence brain AII. In this study, we hypothesized that brain AII is influenced by circulating factors. To investigate the role of blood pressure and plasma AII in brain AII level, we studied the effect of an antihypertensive drug on brain AII in two-kidney, one-clip (2K1C) and spontaneously hypertensive (SHR) rats. 2. Hydralazine (20 mg/kg per day) and vehicle (water) were given to 2K1C rats between 2 and 6 weeks after operation and SHR for 4 weeks. In addition, vehicle was applied to sham operated rats and Wistar-Kyoto (WKY) rats. Brain and plasma AII was measured by a highly sensitive radioimmunoassay coupled with high performance liquid chromatography. 3. Hydralazine treatment effectively lowered blood pressure to the same level of sham-operated and WKY rats. 2K1C rats showed significantly higher plasma AII than sham rats, but hydralazine treatment did not show any change in plasma AII. Brain AII in the hypothalamus region of 2K1C rats showed a significantly higher level than sham rats. Interestingly, hydralazine treatment diminished this increase in brain AII. In contrast, SHR showed higher brain AII levels in the hypothalamus, brainstem and cerebellum than in WKY rats, whereas there was no significant change in plasma AII concentration between SHR and WKY rats. In contrast to the results found in 2K1C rat experiments, hydralazine treatment failed to decrease brain AII levels despite lowered blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
R
R
Morishita
J
J
Higaki
Y
Y
Nakamura
M
M
Aoki
K
K
Yamada
A
A
Moriguchi
H
H
Rakugi
N
N
Tomita
S
S
Tomita
H
H
Yu
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D006830:Hydralazine / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism*; D006978:Hypertension, Renovascular / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects
D000959:Antihypertensive Agents; D000804:Angiotensin II; D006830:Hydralazine