Effects of propofol on substance P-induced relaxation in isolated human omental arteries and veins.
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.
Bodelsson
G
G
Department of Obstetrics and Gynaecology, University Hospital, Malmö, Sweden.
Sandström
K
K
Wallerstedt
S M
SM
Hidestâl
J
J
Törnebrandt
K
K
Bodelsson
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000494:pharmacology; D009852:Omentum / Q000098:blood supply*; D015742:Propofol / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects / Q000502:physiology
D018686:Anesthetics, Intravenous; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D013373:Substance P; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester; D015742:Propofol