Inhibitors of nitric oxide synthase enhance rat ileum contractions induced by ricinoleic acid in vitro.
The effects of NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), inhibitors of nitric oxide (NO) synthase, were studied on ricinoleic acid-evoked contractions in rat isolated ileum. Ricinoleic acid (10(-5) to 10(-4) M) caused a concentration-dependent contraction. Addition of L-NAME (30-300 microM) or L-NMMA (30-300 microM) to the Tyrode's solution increased in a concentration-dependent fashion the amplitude of the ricinoleic acid-evoked responses. L-Arginine (900 microM), a natural substrate of NO synthase, but not D-arginine (900 microM), counteracted the effect of L-NAME (300 microM). The potentiating effect of L-NAME was also prevented by sodium nitroprusside (0.1-1 microM), a generator of NO. These results provide evidence that endogenous NO may modulate the contraction of rat ileum induced by ricinoleic acid. As the contraction induced by ricinoleic acid is not blocked by tetrodotoxin (0.6 and 6.0 microM) the contractile effect of ricinoleic acid results mainly from a direct action on the smooth muscle.
Izzo
A A
AA
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Mascolo
N
N
Viola
P
P
Capasso
F
F
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D051381:Rats; D017208:Rats, Wistar; D012277:Ricinoleic Acids / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D019323:omega-N-Methylarginine
D012277:Ricinoleic Acids; D019323:omega-N-Methylarginine; D013779:Tetrodotoxin; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C030521:ricinoleic acid; D019331:NG-Nitroarginine Methyl Ester