Hyporesponsiveness to nitrovasodilators in rat aorta incubated with endotoxin and L-arginine.
We studied the effect of L-arginine on relaxation responses to sodium nitroprusside or SIN-1 (3-morpholinosydonimine-N-ethyl-carbamine) in the rat thoracic aorta incubated with endotoxin. Sodium nitroprusside or SIN-1 produced a reproducible relaxation in the aorta incubated for 12 h with endotoxin. However, the response to both nitrovasodilators was remarkably attenuated when the aorta was preincubated for 12 h with endotoxin and L-arginine. D-Arginine could not substitute for L-arginine. The attenuated response to sodium nitroprusside or SIN-1 was partially restored by the inhibition of nitric oxide (NO) production with N omega-nitro-L-arginine. Cycloheximide prevented the inhibitory effect of preincubation with L-arginine. These results suggest that the prolonged exposure to muscle-derived NO induces hyporesponsiveness to nitrovasodilators.
Department of Pediatrics, Fukui Medical School, Japan.
S
S
Tsuchida
M
M
Hiraoka
M
M
Sudo
I
I
Muramatsu
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001120:Arginine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004731:Endotoxins / Q000494:pharmacology*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D004731:Endotoxins; D014665:Vasodilator Agents; D009599:Nitroprusside; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine