Effect of gonadectomy on the metabolism of arachidonic acid in isolated kidney of a rat model of metabolic syndrome

17βEstradiol Modulates Perfusion Pressure and Expression of 5-LOX and CYP450 4A in the Isolated Kidney of Metabolic Syndrome Female Rats

“…The Fallopian tubes were ligated and cut below the ligature. After the extirpation, the incision was sutured [ 4 ].…”

“…Changes in the PP produced by AA were calculated by taking the mean of the pulsatile trace before the administration of AA and the mean of the trace at the maximal PP value after injection of AA. Data are expressed as changes (Δ) of PP in mmHg [ 4 ]. After at least 15 minutes of perfusion and once a stable PP had been obtained, vasoconstrictor responses to AA 4 μ g/mL·min were determined in the absence and presence of 10 μ mo/L Baicalein (5-LOX pathway inhibitor), 5 μ mo/L Miconazole (pathway inhibitor of CYP450 4A), or 10 μ mo/L Indomethacin (COX isoforms pathway inhibitor).…”

“…In nephropathy models in humans and animals, males with MS exhibit a faster decline in renal function than females. The incidence of MS is lower in premenopausal women and it increases after menopause, when estrogen levels dramatically decrease accelerating the progression of atherosclerosis and kidney diseases [ 4 ]. These differences could be explained by the presence of estradiol (E 2 ).…”

“…The synthesis of eicosanoids is mediated by three enzymatic pathways: cyclooxygenase isoforms (COX-1 and COX-2), lipoxygenase (5-, 12-, and 15-LOX), and cytochrome P450 (CYP450 4A, 2C2, 2C6, and 2J2). Eicosanoids include prostanoids derived from the COX pathways, leukotrienes synthetized by the LOX pathways, and hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) derived from the CYP450 4A and 2C2, 2C6, and 2J2 pathways, respectively [ 4 ].…”

“…Previous research in our laboratory showed that the increase in perfusion pressure (PP) in isolated kidney of MSovx rats in presence of 4 μ g AA was related to a decrease in COX-1 and overexpression of COX-2 and that replacement with E 2 reverted it [ 4 ]. Other studies have shown that E 2 blocks the increased expression of COX-2 in the vessels and that it inhibits the increased production of prostaglandin E 2 in response to inflammatory stimuli [ 14 ].…”