Role of Sex Steroids in Modulating Tumor Necrosis Factor Alpha-Induced Changes in Vascular Function and Blood Pressure

Abstract

We previously showed that the infusion of tumor necrosis factor alpha (TNF-alpha) induces hypertension and vascular dysfunction in late pregnant but not virgin rats. In the present study, we tested the hypothesis that levels of ovarian hormones to mimic pregnancy are required for TNF-alpha-induced changes in vascular function and blood pressure in rats. Twenty-one-day-release pellets containing 17beta-estradiol, progesterone, or both were implanted in ovariectomized (OVX) rats. Sham OVX rats were used as controls. Twelve days after implantation, TNF-alpha or vehicle was infused via osmotic minipumps (days 12 to 17). On day 18, mean arterial pressure was measured, and animals were sacrificed to assess vascular function. Average estrogen and progesterone levels across all groups were 106 +/- 6 pg/mL and 88 +/- 5 ng/mL, respectively. The level of TNF-alpha was 41 +/- 7 pg/mL compared with OVX rats infused with vehicle (4 +/- 1 pg/mL). The results show that TNF-alpha did not cause elevated mean arterial pressure in OVX rats with increased estrogen, progesterone, or both. Vascular responses to the endothelium-dependent and independent agonists, acetylcholine and sodium nitroprusside, were also unchanged. Phenylephrine-induced contraction was moderately but significantly increased at the highest concentrations (10(-4) M) only in TNF-alpha-infused rats. These data suggest that increased ovarian hormones to the levels observed during pregnancy are not sufficient to promote TNF-alpha-induced increases in blood pressure or vascular dysfunction.