Effect of olmesartan and pravastatin on experimental cerebral aneurysms in rats.
The major initiation process of intracranial aneurysms is thought to involve endothelial dysfunction due to hemodynamic stress. Angiotensin II type 1 receptor blockers and statins improve vascular endothelium function. The effects of olmesartan and pravastatin were investigated on the development of experimental aneurysms in rats. Eighty-three rats underwent aneurysm induction. Seven groups of 10-14 rats were treated with low or high dose olmesartan, low or high dose pravastatin, low doses of olmesartan and pravastatin, hydralazine, or no drug (control) for 12weeks, when rats were sacrificed for vascular corrosion casting and scanning electron microscopy. Aneurysmal changes at the anterior cerebral-olfactory artery bifurcation were divided into stages 0 (no abnormality) to III (saccular aneurysm). Systolic arterial blood pressure was elevated over 170mmHg in the control, low dose pravastatin, and high dose pravastatin groups, but not in the other groups. The control group demonstrated aneurysmal changes in 100% and stage III in 50% of rats. Aneurysmal changes were observed in most rats in the other groups, but the incidence of stage III was 10% or less. The staging pattern showed significant differences between the groups (P=0.028). Pravastatin reduced both stages III and II+III and olmesartan ameliorated stage III, implying that these may prevent aneurysmal formation through acting on different steps. (209 words).
Kimura
Naoto
N
Department of Neuroendovascular therapy, Tohoku University Graduate School of Medicine, Sendai, Japan.
Shimizu
Hiroaki
H
Eldawoody
Hany
H
Nakayama
Toshio
T
Saito
Atsushi
A
Tominaga
Teiji
T
Takahashi
Akira
A
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002941:Circle of Willis / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016319:Corrosion Casting; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D006830:Hydralazine / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D002532:Intracranial Aneurysm / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008855:Microscopy, Electron, Scanning; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; D014665:Vasodilator Agents; D006830:Hydralazine; C437965:olmesartan; D017035:Pravastatin