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Effect of ovariectomy in the renal effects of NFkB inhibition on aged DOCA hypertensive female
Author(s) -
Fortepiani Lourdes A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.941.11
Subject(s) - endocrinology , medicine , renal function , kidney , hormone
The loss of ovarian function with aging is associated with increases in BP and renal dysfunction. Mineralocorticoid hypertension (DOCA) is associated with increased NF‐kB activation that regulates genes involved in BP and renal function regulation. Young female (F) DOCA rats exhibit hypertension and renal injury that is exacerbated after ovariectomy (ovx). Since NFkB inhibition lowered BP in male DOCA rat, we hypothesize that NFkB inhibition will attenuate the development of hypertension and renal damage in old ovx DOCA in a greater extent than in old F‐DOCA rats. F‐DOCA rats were ovx or sham operated at 9 mos of age and treated with NFkB inhibitor (PDTC) for 2 weeks. Ovx at 9 mos did not alter BP (F: 147.1 ± 4.2 vs Ovx: 145.4 ± 5.1mmHg) but increased glomerular filtration rate (GFR), and decreased renal vascular resistance (RVR) and proteinuria. Blockade of NFkB increased GFR (1.32 ± 0.1 vs 1.6 ± 0.1 ml/min/g) and decreased RVR and P in female (29.9 ± 0.8 vs 16.6 ± 1.5ml/min/g and 14.1 ± 0.3 vs 2.5 ± 1.0g/ml); however it decreased GFR (1.6 ± 0.1 vs 1.3 ± 0.1 ml/min/g), and increased RVR and P in ovx (23.9 ± 2.9 vs 44.8 ± 6.2 and 0.3 ± 0.01 vs 6.3 ± 1.4g/ml). These results suggest that the beneficial effects of NFkB inhibition in the kidney of aged DOCA rats are mediated by ovarian sex hormones and when ovaries are removed, the renal effects of NFkB inhibition result detrimental rather than beneficial. This work was supported by NIH AG029250‐01 award