Endothelium independent protective effect of NG-monomethyl-L-arginine on endotoxin-induced alterations of vascular reactivity.
The effects of NG-monomethyl-L-arginine (NMMA), a specific inhibitor of nitric oxide (NO) synthesis was tested on the endotoxin-induced alterations of alpha-adrenoceptor function. In isolated aorta, there was no significant difference in the tension induced by phenylephrine (PE, 10 microM) on rings removed from control and endotoxin injected rats (10 mg/kg, ip). However, a lack of tonicity of the contraction was observed in rings of shocked rats (8 +/- 2.9 and 86 +/- 4.6% relaxation at 105 min for sham and shocked rings respectively). The gradual tension decrease to PE was more potent in rings possessing endothelial cells. However, in both preparations, the loss of tonicity was significantly inhibited by NMMA (30 microM). In endothelium-free rings, L-arginine (100 microM) potentiated the loss of tonicity to PE and reversed the inhibitory effect of NMMA. NMMA, like methylene blue, was also able to restore the PE-contraction. The results indicate that the endotoxin-induced alterations of vascular reactivity may be due, in part, to NO formation from L-arginine independent of the endothelium.
Auguet
M
M
Institut Henri Beaufour Research Labs., Les Ulis, France.
Guillon
J M
JM
Delaflotte
S
S
Etiemble
E
E
Chabrier
P E
PE
Braquet
P
P
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D004731:Endotoxins / Q000633:toxicity*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009566:Nitrates / Q000378:metabolism; D017942:Nitric Acid; D051381:Rats; D011919:Rats, Inbred Strains; D019323:omega-N-Methylarginine
D004731:Endotoxins; D009566:Nitrates; D019323:omega-N-Methylarginine; D017942:Nitric Acid; D001120:Arginine; D008751:Methylene Blue