Valsartan improves the lower limit of cerebral autoregulation in rats.
The effects of angiotensin II type 1 receptor blockers (ARBs) on cerebral blood flow (CBF) autoregulation have not been fully clarified. Thus, we examined the acute effect of valsartan, the most selective ARB, on CBF autoregulation in spontaneously hypertensive rats. Intravenous administration of valsartan (0.3 mg/kg) reduced the mean arterial pressure (MAP) from 184+/-5 (mean+/-SEM) to 174+/-5 mmHg (p<0.001) without affecting CBF as measured by laser-Doppler flowmetry. The lower limit of CBF autoregulation (the MAP at which the CBF was 80% of the baseline value) in the valsartan-treated group (122+/-3 mmHg) was significantly lower than that in the control group (135+/-4 mmHg, p<0.05). Reverse transcribed-polymerase chain reaction and immunohistochemical staining demonstrated that both angiotensin II type 2 receptors and angiotensin II type 1 receptors (AT1Rs) were expressed in endothelial and smooth muscle cells of the rat cerebral arteries. These results suggest that specific inhibition of AT1Rs in the cerebral circulation causes the leftward shift of the lower limit of autoregulation.
Takada
Junichi
J
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ibayashi
Setsuro
S
Ooboshi
Hiroaki
H
Ago
Tetsuro
T
Ishikawa
Eiichi
E
Kamouchi
Masahiro
M
Kitazono
Takanari
T
Iida
Mitsuo
M
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013687:Telencephalon / Q000098:blood supply* / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine