Ovariectomy Causes Overexpression of Renal Na⁺,K⁺-ATPase and Sodium-Sensitive Hypertension in Adult Wistar Rats

Abstract

We investigated the effect of ovariectomy(oVx) on renal and systemic hemodynamic, electrolyte excretion and total and dephosphorylated Na(+),K(+)-ATPase α1 subunit (t-d-NKA) in normotensive Wistar rats under a normal sodium (NS, 0.24%) or high sodium (HS, 1%) intake versus intact female (IF). On NS intake, t-d-NKA was higher in oVx rats and overexpressed in the thick ascending limbs (P < .01 vs. IF) and renal plasma flow was increased. On HS intake, oVx rats maintained a greater dephosphorylated NKA, excreted less sodium, and developed arterial hypertension (134 ± 4 vs. IF 112 ± 5 mm Hg, P < .05). Sodium load caused salt-sensitive hypertension in oVx Wistar rats.

Ovariectomy and high salt increase blood pressure and alter sodium transport proteins in peripheral blood mononuclear cells of adult Wistar rats

“…In agreement with our previous findings (Di Ciano et al., 2013), the present results show that oVx adult Wistar rats when exposed to high sodium load are not able to excrete sodium as IF HS rats do. Consequently, while IF HS rats remain normotensive, oVx HS rats develop salt‐sensitive hypertension.…”

“…In previous work, we found that ovariectomized adult Wistar rats under high salt (HS) intake develop HT (Di Ciano et al., 2013). Thus, the absence of female sex hormones together with high sodium induced an increase in BP in this model of salt‐sensitive hypertension.…”

Defective renal dopamine function and sodium-sensitive hypertension in adult ovariectomized Wistar rats: role of the cytochromeP-450 pathway

“…Two days before clearance studies subgroups of HS rats (IF and oVx) were treated with the D1-like receptor antagonist SCH 23390 [1 mg/kg body wt sc twice a day; R (ϩ)-SCH 23390 hydrochloride, Sigma-Aldrich, St. Louis, MO] or with vehicle (normal saline). Animals were anesthetized with Inactin (50 mg/kg body wt ip) and surgically prepared for a renal clearance experiment as described previously (13). The trachea was cannulated to facilitate breathing.…”

“…Further results showed that ovariectomy causes an overexpression of the total Na ϩ -K ϩ -ATPase (t-NKA) ␣1-subunit in tubular epithelial cells as well as an altered balance between the phosphorylation/dephosphorylation of NKA to a more dephosphorylated (more active) state. As a consequence, when ovariectomized (oVx) rats were shifted from a normal-sodium diet (NS) to a high-sodium diet (HS), they were unable to achieve a normal sodium balance and developed salt-sensitive hypertension (13).…”

“…Based on data from other authors and on our previous findings that 1) an increase in renal DA production and its normal tubular function are necessary to eliminate the sodium overload under HS in intact rats (1); 2) stimulation of DA receptors activates PKC, which phosphorylates NKA, causing the inhibition of its activity (31,32); and 3) altered NKA phosphorylation at the PKC site was found in oVx rats on HS intake together with the development of salt-sensitive hypertension (13), we hypothesized that the renal DA system could be involved in the altered sodium balance in oVx rats on HS.…”