Rosiglitazone Decreases Blood Pressure in Female Dahl Rats: Role of Nitric Oxide and Oxidative Stress

Abstract

In women the prevalence of hypertension (HT) and salt‐sensitivity of blood pressure (BP) increases after menopause (PM). The peroxisome proliferator activator receptor gamma agonist, rosiglitazone (RO), reduces BP in humans and animals, including male Dahl salt‐sensitive rats (DS). We tested the hypothesis that RO decreases BP in intact (Int) and ovariectomized (Ovx) female DS by increasing nitric oxide (NO) and decreasing oxidative stress (OS). Int and Ovx DS (10 weeks; n=15/group) received low salt diet (LS: 0.3% NaCl) or LS+RO (100mg/kg diet) for 1 week and then challenged for 1 week to high salt (HS: 8% NaCl) or HS+RO. Urinary Nitrate/nitrite (N/N) and F2‐isoprostanes (F2Ip) were assessed on HS. On LS, telemetric BP was similar in Int and Ovx, and RO decreased BP to similar levels. On HS, BP increased to higher levels in Ovx than Int and RO decreased BP to similar levels in Int and Ovx. RO increased N/N only in Ovx. F2Ip were lower in Ovx than Int and not affected by RO. Our data suggest that in Ovx on HS, RO protects against the greater increase in BP, possibly by increasing NO bioavailability, and that OS plays no role in salt‐sensitivity of BP in female DS. RO may be a new therapeutic approach for treating HT in PM women (supported by NIH HL 66072, AHA 0725561B)