The action of sevoflurane on vascular smooth muscle of isolated mesenteric resistance arteries (part 1): role of endothelium.
BACKGROUND
The direct action of sevoflurane on systemic resistance arteries is not fully understood.


METHODS
Isometric force was recorded in isolated rat small mesenteric arteries.


RESULTS
Sevoflurane (2-5%) enhanced contractile response to norepinephrine only in the presence of endothelium, but inhibited it in its absence. Sevoflurane still enhanced the norepinephrine response after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of either endothelin-1 ET-1), angiotensin-II, or sevotonin receptors. Sevoflurane (3-5%) inhibited contractile response to potassium chloride only in the absence of endothelium but did not influence it in its presence. In the endothelium-intact strips, inhibition of the norepinephrine response, which was enhanced during application of sevoflurane, was observed after washout of sevoflurane and persisted for approximately 15 min. In the endothelium-denuded strips, the inhibition of norepinephrine response was similarly prolonged after washout of sevoflurane. However, no significant inhibitions of potassium chloride response were observed after washout of sevoflurane in both the endothelium-intact and the endothelium-denuded strips.


CONCLUSIONS
The action of sevoflurane on norepinephrine contractile response consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. In the presence of endothelium, the former predominates over the latter, enhancing the norepinephrine response. The endothelium-independent component persisted after washout of sevoflurane, leading to prolonged inhibition of the norepinephrine response. The mechanisms behind the sevoflurane-induced inhibition of norepinephrine response are at least in part different from those behind its inhibition of potassium chloride response. Nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin-II, and serotonin are not involved in the vasoconstricting action. (Key words: Halogenated volatile anesthetics; sympathetic nervous system; systemic hypotension; vascular endothelium.)
Izumi
K
K
Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Akata
T
T
Takahashi
S
S
D000109:Acetylcholine / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000077149:Sevoflurane; D011189:Potassium Chloride; D000109:Acetylcholine; D009638:Norepinephrine