The goals of this in vitro study were to investigate effects of etomidate on endothelium-dependent relaxation induced by acetylcholine in rat aorta, and to elucidate the associated cellular mechanism. In endothelium-intact rings precontracted with phenylephrine 10−6 M, dose-response curves for acetylcholine (10−9 to 10−5 M) and calcium ionophore (10−9 to 10−6 M) were generated in the presence and absence of etomidate (5×10−6, 10−5 M). In endothelium-intact or -denuded rings precontracted with phenylephrine 10−6 M, sodium nitroprusside (10−9 to 10−6 M) dose-response curves were generated in the presence and absence of etomidate (10−5 M). Etomidate (5×10−6, 10−5 M) produced a significant rightward shift in the dose-response curves induced by acetylcholine (receptor-mediated endothelium-dependent agonist) and calcium ionophore A23187 (non receptor-mediated endothelium-dependent agonist). Etomidate (10−5 M) had no effect on sodium nitroprusside (endothelium-independent nitric oxide donor)-induced vasorelaxant response in both endothelium-intact and -denuded rings. These results indicate that etomidate at clinically relevant concentrations attenuates endothelium-dependent relaxation induced by acetylcholine by an acting at a site distal to the endothelial muscarinic receptor, but proximal to guanylate cyclase activation of vascular smooth muscle in rat aorta.
Our study was designed to determine serum uric acid levels and establish clinically useful cutoff values for the diagnosis of preeclampsia in twin and triplet gestations. We reviewed the medical records of 129 multiple gestations with serum uric acid levels available. Fifty-five twin gestations were complicated by preeclampsia, 51 were not. Fifteen triplet gestations were complicated by preeclampsia, and 8 were not. Preeclampsia was defined as a persistent blood pressure > or =140/90 mmHg, and proteinuria, or elevated liver enzymes, thrombocytopenia, or eclamptic seizure. Receiver operating characteristic curves were generated for twin and triplet gestations. Serum uric acid levels at different stages of gestation in twin gestations were determined. Maternal serum uric acid levels in preeclamptic twin and triplet gestations were significantly higher than those in nonpreeclamptics. Serum uric acid levels at varying gestational ages were significantly higher in preeclamptic twin gestations than in nonpreeclamptics. Maternal serum uric acid levels of 6.3 mg/dL and 6.8 mg/dL were found to be the most useful cutoff values for the diagnosis of preeclampsia in twin and triplet gestations, respectively. We conclude that compared to nonpreeclamptics, preeclamptic women with multiple gestations had significantly higher serum uric acid levels. Mean serum uric acid levels based on gestational age should be justified for the diagnosis of preeclampsia in multiple gestations.
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