ABSTRACT
To elucidate if an effect of propofol on endothelium-dependent relaxation could contribute to propofol-induced vasodilation, smooth muscle relaxation of isolated human omental artery and vein segments precontracted by endothelin-1 were measured. Substance P induced a concentration-dependent relaxation (mean +/- SEM) in both artery (63 +/-8.4% of precontraction, n = 9) and vein (60+/-11%, n = 7). The relaxation was enhanced by 10(-6) M propofol (artery, 72+/-9.5%, n = 9; vein, 81+/-12%, n = 7) but not affected by 10(-7), 10(-5) and 10(-4) M propofol. In the presence of Nomega-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 10(-6) M propofol still enhanced the substance P-induced relaxation in arteries but not veins, whereas 10(-4) M propofol inhibited the relaxation in both arteries (rightward shift of the concentration-response curve) and veins (28+/-7.5%, n = 8). In the presence of potassium chloride (to prevent hyperpolarization), the enhancement of substance P-induced relaxation by 10(-6) M propofol was abolished in both arteries and veins whereas 10(-5) and 10(-4) M propofol reduced the relaxation in arteries (38+/-13% at 10(-5) M, n = 6; 30+/-11% at 10(-4) M, n = 6) but not in veins. These results demonstrate that propofol, at lower, clinically relevant concentrations, promotes endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins.
Subject(s)
Anesthetics, Intravenous/pharmacology , Omentum/blood supply , Propofol/pharmacology , Substance P/pharmacology , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Adult , Aged , Aged, 80 and over , Arteries/drug effects , Arteries/physiology , Dose-Response Relationship, Drug , Endothelin-1/pharmacology , Endothelium, Vascular/physiology , Enzyme Inhibitors/pharmacology , Female , Humans , In Vitro Techniques , Male , Middle Aged , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitroglycerin/pharmacology , Veins/drug effects , Veins/physiologyABSTRACT
The optimal dosage of anaesthetic agents may be difficult. Not only does the intensity of surgical stimuli vary during a surgical procedure, but drug sensitivity varies between subjects exposed to comparable stimuli. Moreover, clinically monitored body reactions do not always reflect the balance between central nervous system effects of the surgical stimuli and of the anaesthetic agent. Therefore, the specialist in anaesthesiology requires access to additional methods of monitoring to enable dosage to be optimised for each patient, minute by minute, thus improving the chances of maintaining an appropriate depth of anaesthesia. Two electro-encephalographic techniques are presented in the article, and aspects of under- and over-dosage of anaesthetic agents are discussed.
