The role of induction of nitric oxide synthesis in the altered responses of jugular veins from endotoxaemic rabbits.
1. Endotoxaemia is characterized by hypotension, peripheral vasodilatation and a reduced response to vasoconstrictors. Clinical studies have indicated that venodilatation contributes to the haemodynamic changes, although there is no direct evidence for abnormal venous reactivity. In the present study, the role of nitric oxide (NO) in modifying the responses of rabbit isolated jugular veins was examined in vitro, 4 h after intravenous injection of endotoxin. 2. Treatment with endotoxin reduced the contractile response to the thromboxane-mimetic, 9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha (U-46619). This affect was endothelium-independent. The response was partially restored by the NO synthase inhibitor. NG-monomethyl-L-arginine (L-NMMA 300 microM). 3. Jugular veins from control animals did not contract to L-NMMA whereas those from endotoxin-treated animals showed concentration-dependent contractions to L-NMMA. The contractions produced by L-NMMA were reversed by L-arginine but not by D-arginine. Treatment of the animals with dexamethasone (4 mg kg-1) 1 h prior to administration of endotoxin significantly attenuated the response to L-NMMA. 4. The response to sodium nitroprusside did not differ significantly between veins from control and endotoxin-treated animals. Endothelial denudation did not alter the sensitivity of the veins to sodium nitroprusside. Acetylcholine produced endothelium-dependent relaxations which were similar in veins from control and endotoxin-treated animals. 5. The results of this study demonstrate that intravenous administration of endotoxin induces hyporesponsiveness to U-46619 in jugular veins. This effect is mediated, at least in part, by the induction of NO synthesis in smooth muscle. The induction is prevented by prior treatment with dexamethasone.
Vallance
P
P
Wellcome Research Laboratories, Beckenham, Kent.
Palmer
R M
RM
Moncada
S
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001427:Bacterial Toxins / Q000633:toxicity*; D004731:Endotoxins / Q000633:toxicity*; D004768:Enterotoxins / Q000633:toxicity*; D005260:Female; D066298:In Vitro Techniques; D007601:Jugular Veins / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011817:Rabbits; D012485:Salmonella typhi; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine
D001427:Bacterial Toxins; D004731:Endotoxins; D004768:Enterotoxins; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; C027952:salmonella toxin; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D000109:Acetylcholine