POSTNATAL CHANGES IN MECHANISMS MEDIATING ACETYLCHOLINE-INDUCED RELAXATION IN PIGLET FEMORAL ARTERIES

We studied the nitric oxide-cGMP pathway in endothelium-dependent rela xation in femoral arterial rings from piglets at different postnatal a ges. Responses to acetylcholine (ACh) and sodium nitroprusside (SNP) w ere examined in phenylephrine-precontracted rings from newborn (10-22- h) and 7 d (7-10-d)-old piglets. Relaxant responses were investigated in endothelium-denuded rings and endothelium-intact controls, and in e ndothelium-intact rings incubated with the nitric oxide synthase (NOS) inhibitor N-G-monomethyl-L-arginine acetate (L-NMMA), indomethacin, o r the superoxide anion generator 6-anilinoquinoline-5,8-quinone (LY835 83). Arterial rings from both age groups relaxed to a similar degree i n response to ACh. Relaxation in rings from newborn piglets was insens itive to NOS inhibition by L-NMMA, whereas in artery rings from 7-d-ol d piglets, the relaxant response was significantly inhibited by L-NMMA . Incubation with LY83583 gave an inhibition of ACh-induced relaxation very similar to chat of L-NMMA. Incubation with indomethacin had no s ignificant effect on ACh-induced relaxation in either age group. Arter y rings from both age groups relaxed 100% to SNP; the 7-d-old group wa s more sensitive than the newborn. NOS inhibition potentiated SNP-indu ced relaxation in both groups, but the potentiating effect was of grea ter magnitude in the newborn. Our results indicate a difference in the mechanism(s) underlying ACh-induced relaxation in the femoral artery from newborn and 7-d-old piglets, with an intact relaxant response in rings from the newborn despite NOS inhibition. The SNP results indicat e a down-regulated soluble guanylate cyclase in the newborn, possibly related to a difference in basal NO release between the two age groups .