Sevoflurane and the feto-placental vasculature: the role of nitric oxide and vasoactive eicosanoids.
BACKGROUND
The effects and mechanisms of action of volatile anesthetics on the feto-placental vasculature are not known. We aimed to quantify the vasoactive effects of sevoflurane and determine the role of nitric oxide (NO) and of vasoactive eicosanoids in mediating these effects in isolated human chorionic plate arterial rings.


METHODS
Quadruplicate ex vivo human chorionic plate arterial rings were used in all studies. Series 1 quantified the vasodilation produced by sevoflurane in rings preconstricted with the thromboxane analog U46619. Series 2A-C examined the role of NO in sevoflurane-mediated vasodilation. In separate experiments, we examined the potential for the nonspecific NO inhibitors, L-NAME, L-nMMA, and the inactive D-NAME, to modulate the vasodilation produced by sevoflurane. Series 2D determined whether sevoflurane altered vascular smooth muscle sensitivity to exogenous NO. Series 3A-D examined the role of vasoactive eicosanoids in sevoflurane-mediated vasodilation. In separate experimental series, we examined whether the nonspecific cyclooxygenase inhibitor, indomethacin, or the 5-lipoxygenase inhibitor, nordihydroguaiaretic acid, modulated sevoflurane-mediated vasodilation.


RESULTS
Sevoflurane produced dose-dependent vasodilation of preconstricted chorionic plate arterial rings, with mean ring vasodilation increasing from 15 +/- 7% at 2% sevoflurane to 67 +/- 17% (mean +/- sd) at 8% sevoflurane. Blockade of NO synthase did not attenuate the vasodilator effects of sevoflurane. Sevoflurane did not alter smooth muscle sensitivity to NO. Indomethacin augmented sevoflurane vasodilation at 10(-5) M, but not at 10(-6) M. Conversely, nordihydroguaiaretic acid attenuated sevoflurane-mediated vasodilation at 3 x 10(-6) M but not at 3 x 10(-7) M.


CONCLUSIONS
Sevoflurane was a vasodilator in the feto-placental vasculature in this in vitro model. Sevoflurane-mediated vasodilation is NO and cyclooxygenase-independent and appears to be mediated in part via a lipoxygenase generated vasodilator eicosanoid.
Farragher
Rachel
R
Department of Anaesthesia, Clinical Sciences Institute, National University of Ireland.
Maharaj
Chrisen H
CH
Higgins
Brendan D
BD
Crowe
Sharon
S
Burke
Padvaic
P
Laffey
Christopher D
CD
Flynn
Noel M
NM
Laffey
John G
JG
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000098:blood supply*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D008738:Methyl Ethers / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D000077149:Sevoflurane; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D015777:Eicosanoids; D008738:Methyl Ethers; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000077149:Sevoflurane; D009637:Masoprocol; D007213:Indomethacin