Propofol-induced relaxation of rat mesenteric arteries: evidence for a cyclic GMP-mediated mechanism.
Experiments were designed to evaluate whether guanosine 3',5'-cyclic monophosphate (cGMP)-mediated mechanisms contribute to vasodilation via propofol in rat mesenteric resistance arteries. Ring segments were suspended in the myograph system for isometric tension recording, and responses to propofol were tested in the presence and absence of methylene blue (MB), an inhibitor of guanylate cyclase. At concentrations > or = 1 microM, propofol caused concentration-dependent relaxation of vessel rings precontracted with U46619 (a thromboxane analog). The effect was not affected by N-monomethyl-L-arginine (L-NMMA; 50 microM). MB (5 microM) reversed propofol-induced vasodilation by 30% (p < 0.001). In contrast, MB has no effect on nifedipine-inhibited vasocontraction. The propofol-induced relaxation was further tested in rings incubated in Ca2+-free solution. U46619-induced contractions were significantly reduced by propofol (40 microM) but not by nifedipine (1 microM). Propofol reduced to a similar degree the contractions obtained to exogenously added calcium chloride in the absence and the presence of MB. Furthermore, propofol (10-100 microM) increased cGMP content in cultured bovine vascular smooth-muscle cells. Soluble guanylate cyclase inhibitors, such as MB and LY83583, attenuated this effect. This investigation suggests that propofol-induced relaxations in small arteries, in addition to inhibition of calcium influx, are mediated by increases of cGMP in the smooth muscle cells.
Liu
R
R
Department of Research, University Hospital, Basel, Switzerland.
Lang
M G
MG
Lüscher
T F
TF
Kaufmann
M
M
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D008751:Methylene Blue / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*
D006152:Cyclic GMP; D002118:Calcium; D008751:Methylene Blue; D015742:Propofol