Role of endothelium in the action of isoflurane on vascular smooth muscle of isolated mesenteric resistance arteries

Background: It is believed that isoflurane decreases blood pressure predomi nantly by decreasing systemic vascular resistance with modest myocardial de pression. Nevertheless, little information is available regarding the direc t action of isoflurane on systemic resistance arteries. Methods: With use of the isometric force recording method, the action of is oflurane on contractile response to norepinephrine, a neurotransmitter that plays a central role in sympathetic maintenance of vascular tone in vivo, was investigated in isolated rat small mesenteric arteries. Results: In the endothelium-intact strips, the norepinephrine response was initially enhanced after application of isoflurane (2-5%), but it was subse quently almost normalized to the control level during exposure to isofluran e. However, the norepinephrine response was notably inhibited after washout of isoflurane. In the endothelium-denuded strips, the norepinephrine respo nse was gradually inhibited during exposure to isoflurane ( greater than or equal to 3%), and the inhibition was prolonged after washout of isoflurane . The isoflurane-induced enhancement of norepinephrine response was still o bserved after inhibitions of the nitric oxide, endothelium-derived hyperpol arizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of endothelin-1, angiotensin-II, and serotonin receptors; however, it was prevented by superoxide dismutase. Conclusions: In isolated mesenteric resistance artery, the action of isoflu rane on contractile response to norepinephrine consists of two distinct com ponents: an endothelium-dependent enhancing component and an endothelium-in dependent inhibitory component. During exposure to isoflurane, the former c ounteracted the latter, preventing the norepinephrine response from being s trongly inhibited. However, only the endothelium-independent component pers ists after washout of isoflurane, causing prolonged inhibition of the norep inephrine response. Superoxide anions may be involved in the enhanced respo nse to norepinephrine.