The action of sevoflurane on vascular smooth muscle of isolated mesentericresistance arteries (part 1) - Role of endothelium

Background: The direct action of sevoflurane on systemic resistance arterie s is not fully understood, Methods: Isometric force was recorded in Isolated rat small mesenteric arte ries, Results: Sevoflurane (2-5%) enhanced contractile response to norepinephrine only in the presence of endothelium, but inhibited it in its absence. Sevo flurane still enhanced the norepinephrine response after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase a nd lipoxygenase pathways, or after blockade of either endothelin-1 ET-1), a ngiotensin-II, or sevotonin receptors, Sevoflurane (3- 5%) inhibited contra ctile response to potassium chloride only in the absence of endothelium but did not influence it in its presence. In the endothelium-intact strips, in hibition of the norepinephrine response, which was enhanced during applicat ion of sevoflurane, was observed after washout of sevoflurane and persisted for approximately 15 min. In the endothelium-denuded strips, the inhibitio n of norepinephrine response was similarly prolonged after washout of sevof lurane, However, no significant inhibitions of potassium chloride response were observed after washout of sevoflurane in both the endothelium-intact a nd the endothelium-denuded strips. Conclusions: The action of sevoflurane on norepinephrine contractile respon se consists of endothelium-dependent vasoconstricting and endothelium-indep endent vasodilating components, In the presence of endothelium, the former predominates over the latter, enhancing the nonrepinephrine response. The e ndothelium-independent component persisted after washout of sevoflurane, le ading to prolonged inhibition of the norepinephrine response. The mechanism s behind the sevoflurane-induced inhibition of norepinephrine response are at least in part different from those behind its inhibition of potassium ch loride response. Nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin-I I, and serotonin are not involved in the vasoconstricting action.