title: Increase in body Na+/water ratio is associated with cerebral aneurysm formation in oophorectomized rats.
abstract: The incidence of cerebral aneurysms is higher in women than in men, especially postmenopause. Although hypertension is thought to be associated with a high incidence of stroke, not all patients with unruptured cerebral aneurysms are hypertensive. The possibility of water-free Na(+) storage associated with hypertension has been raised. However, whether the increase in the body Na(+)/water ratio that characterizes water-free Na(+) accumulation is associated with the formation of cerebral aneurysms remains obscure. To examine this relationship, Sprague-Dawley female rats subjected to carotid artery ligation were divided into 3 groups: a high-salt diet group (HSD) without and another with bilateral oophorectomy (HSD/OVX) and a third group that underwent additional renal artery ligation (HSD/OVX/RL). Compared with rats receiving a normal diet (shams), water retention was increased in HSD rats but not in HSD/OVX rats. Interestingly, compared with HSD rats, the incidence of cerebral aneurysms and the body Na(+)/water ratio were significantly higher in HSD/OVX and HSD/OVX/RL rats, independent of hypertension. In their aneurysmal wall, ATP1α2, a subtype of Na(+)/K(+)-ATPase, was downregulated, whereas inflammatory-related molecules were upregulated. Treatment with low-dose olmesartan that did not affect the blood pressure in hypertensive HSD/OVX/RL rats reduced the rate of cerebral aneurysm formation, body Na(+) retention, and the Na(+)/water ratio and upregulated ATP1α2. These results suggest that the increase in the Na(+)/water ratio and a reduction in ATP1α2 may be associated with cerebral aneurysm formation. We provide the new insight that the management of water-free Na(+) is important to prevent their development.
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8503, Japan. nobuhisama@gmail.com
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Matsushita
authors.forename: Keiko T
authors.initials: KT
authors.lastname: Kitazato
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Tada
authors.forename: Manabu
authors.initials: M
authors.lastname: Sumiyoshi
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimada
authors.forename: Kenji
authors.initials: K
authors.lastname: Yagi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kanematsu
authors.forename: Junichiro
authors.initials: J
authors.lastname: Satomi
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagahiro
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001834:Body Water / Q000378:metabolism*; D002339:Carotid Arteries / Q000601:surgery; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D002532:Intracranial Aneurysm / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D008026:Ligation; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000601:surgery; D012964:Sodium / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014882:Water-Electrolyte Balance
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; C437965:olmesartan; D012964:Sodium; C498532:Atp1a2 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase