Abstract TP78: Down-regulation Of Vascular Na+/k+ ATPase In Oophorectomized Rats Feeding A High Salt Diet Is Associated With The Cerebral Aneurysm Formation

Abstract

Background and Purpose— Hypertension is thought to be associated with a high incidence of stroke. However, not all patients with unruptured cerebral aneurysms are hypertensive. In the DOCA-salt rats the increase in body water-free Na+ storage associated with hypertension is suggested. We hypothesized that in oophorectomized rats fed a high salt diet, body water-free Na+ accumulation may be increased, leading to the formation of cerebral aneurysms. To address the relationship between the increase in the body Na+-to-water ratio that characterizes water-free Na+ accumulation and the formation of cerebral aneurysms, we focused on vascular Na efflux pump Na+/K+ ATPase. Methods— Thirteen-week old female Sprague-Dawley rats subjected to carotid artery ligation were fed a high-salt diet and divided into 3 groups; a group without- (HSD) and another with bilateral oophorectomy (HSD/OVX) and a 3rd group that underwent additional renal artery ligation (HSD/OVX/RL) to induce hypertension. Results— Compared to HSD rats, the incidence of cerebral aneurysms and the body Na+-to-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 were down-regulated and renin-angiotensin system- and inflammation related molecules were up-regulated. In HSD/OVX/RL rats treatment with low dose olmesartan up-regulated ATP1α2 without affecting blood pressure and reduced the body Na+-to-water ratio and the incidence of cerebral aneurysm formation. Conclusions— These results suggest that a reduction in the vascular Na efflux pump during excessive salt intake in oophorectomized rats may be associated with the increase in water-free Na+ accumulation directing to cerebral aneurysm formation.