TY - JOUR
T1 - Rosiglitazone reduces blood pressure in female Dahl salt-sensitive rats
AU - Sartori-Valinotti, Julio C.
AU - Venegas-Pont, Marcia R.
AU - LaMarca, Babbette B.
AU - Romero, Damian G.
AU - Yanes, Licy L.
AU - Racusen, Lorraine C.
AU - Jones, Allison V.
AU - Ryan, Michael J.
AU - Reckelhoff, Jane F.
N1 - Funding Information:
The authors would like to thank Huimin Zhang and Stephanie Evans for excellent technical support. J.C. Sartori-Valinotti is recipient of American Heart Association, Greater Southeast Affiliate Postdoctoral Fellowship (0725561B). Licy L. Yanes is recipient of American Heart Association Scientist Development Grant (0830239N). This work was supported by HL51971 , HL69194 , and HL66072 (to JFR) and HL085907 (to MJR) from the National Institutes of Health .
PY - 2010/11
Y1 - 2010/11
N2 - Postmenopausal women (PMW) are at greater risk for salt-sensitive hypertension and insulin resistance than premenopausal women. Peroxisome-proliferator-activated receptor-gamma (PPARγ) agonists reduce blood pressure (BP) and insulin resistance in humans. As in PMW, ovariectomy (OVX) increases salt sensitivity of BP and body weight in Dahl salt-sensitive (DS) rats. This study addressed whether rosiglitazone (ROSI), a PPARγ agonist, attenuates salt-sensitive hypertension in intact (INT) and OVX DS rats, and if so, whether insulin resistance, nitric oxide (NO), oxidative stress, and/or renal inflammation were contributing mediators. Telemetric BP was similar in OVX and INT on low salt diet (0.3% NaCl), but was higher in OVX than INT on high salt (8% NaCl). ROSI reduced BP in OVX and INT on both low and high salt diet, but only attenuated salt sensitivity of BP in OVX. Nitrate/nitrite excretion (NOx; index of NO) was similar in INT and OVX on low salt diet, and ROSI increased NOx in both groups. High salt diet increased NOx in all groups but ROSI only increased NOx in OVX rats. OVX females exhibited insulin resistance, increases in body weight, plasma leptin, cholesterol, numbers of renal cortical macrophages, and renal MCP-1 and osteopontin mRNA expression compared to INT. ROSI reduced cholesterol and macrophage infiltration in OVX, but not INT. In summary, PPARγ activation reduces BP in INT and OVX females, but attenuates the salt sensitivity of BP in OVX only, likely due to increases in NO and in part to reductions in renal resident macrophages and inflammation.
AB - Postmenopausal women (PMW) are at greater risk for salt-sensitive hypertension and insulin resistance than premenopausal women. Peroxisome-proliferator-activated receptor-gamma (PPARγ) agonists reduce blood pressure (BP) and insulin resistance in humans. As in PMW, ovariectomy (OVX) increases salt sensitivity of BP and body weight in Dahl salt-sensitive (DS) rats. This study addressed whether rosiglitazone (ROSI), a PPARγ agonist, attenuates salt-sensitive hypertension in intact (INT) and OVX DS rats, and if so, whether insulin resistance, nitric oxide (NO), oxidative stress, and/or renal inflammation were contributing mediators. Telemetric BP was similar in OVX and INT on low salt diet (0.3% NaCl), but was higher in OVX than INT on high salt (8% NaCl). ROSI reduced BP in OVX and INT on both low and high salt diet, but only attenuated salt sensitivity of BP in OVX. Nitrate/nitrite excretion (NOx; index of NO) was similar in INT and OVX on low salt diet, and ROSI increased NOx in both groups. High salt diet increased NOx in all groups but ROSI only increased NOx in OVX rats. OVX females exhibited insulin resistance, increases in body weight, plasma leptin, cholesterol, numbers of renal cortical macrophages, and renal MCP-1 and osteopontin mRNA expression compared to INT. ROSI reduced cholesterol and macrophage infiltration in OVX, but not INT. In summary, PPARγ activation reduces BP in INT and OVX females, but attenuates the salt sensitivity of BP in OVX only, likely due to increases in NO and in part to reductions in renal resident macrophages and inflammation.
KW - Hypertension
KW - Inflammation
KW - Menopause
KW - Ovariectomy
KW - Oxidative stress
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U2 - 10.1016/j.steroids.2009.10.010
DO - 10.1016/j.steroids.2009.10.010
M3 - Article
C2 - 19883672
AN - SCOPUS:77955927047
SN - 0039-128X
VL - 75
SP - 794
EP - 799
JO - Steroids
JF - Steroids
IS - 11
ER -