Systemic candesartan reduces brain angiotensin II via downregulation of brain renin-angiotensin system.
The renin-angiotensin system has an important function in the regulation of blood pressure as well as in pathophysiological processes in the central nervous system. We examined the effects of the angiotensin receptor blocker candesartan (10 mg kg(-1) per day, p.o.) on brain angiotensin II levels in angiotensin II-infused hypertensive rats. Angiotensin II or vehicle was infused subcutaneously for 14 days in Sprague-Dawley rats. Angiotensin II infusion resulted in increased blood pressure, an effect that was blocked by candesartan treatment. There was no effect of the angiotensin II infusion on Angiotensin II levels in the brain or on blood-brain barrier permeability. Brain tissue angiotensinogen and angiotensin converting enzyme mRNA levels were not changed by angiotensin II infusion but were decreased by candesartan treatment. At 2 weeks of treatment, CV11974, an active form of candesartan, was detectable in the plasma but was not detectable in brain tissue. These data suggest that treatment with candesartan decreases brain angiotensin II by decreasing brain angiotensinogen and angiotensin converting enzyme gene expression.
Pelisch
Nicolas
N
Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University Medical School, Kagawa, Japan. nico@med.kagawa-u.ac.jp
Hosomi
Naohisa
N
Ueno
Masaki
M
Masugata
Hisashi
H
Murao
Koji
K
Hitomi
Hirofumi
H
Nakano
Daisuke
D
Kobori
Hiroyuki
H
Nishiyama
Akira
A
Kohno
Masakazu
M
D000804:Angiotensin II / Q000032:analysis* / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D015536:Down-Regulation; D008297:Male; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000378:metabolism / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; C081643:candesartan