Relative significance of the nitric oxide (NO)/cGMP pathway and K+ channelactivation in endothelium-dependent vasodilation in the femoral artery of developing piglets

Mechanisms mediating endothelium-dependent vasodilation were investigated i n femoral artery rings from <2-day-old (newborn) and 2-week-old piglets. Ba sed on previous results we hypothesized an age difference in the relative c ontribution of nitric oxide(NO)-cyclic 3',5'-guanosine monophosphate (cGMP) and K+ channel-activation to acetylcholine (ACh)-induced vasodilation. Cha nges in vascular tone were studied in organ baths in the absence or presenc e of NO synthase(NOS) inhibition or K+ channel blockade and the intra-arter ial accumulation of cGMP in response to ACh was measured with radioimmunoas say (RIA). In control experiments, relaxant responses to ACh were equal in the two age groups. In the presence of the NOS-inhibitors N-G-monomethyl-L- arginine acetate (L-NMMA, 100 <mu>M) or N-G-nitro-L-aiginine (L-NOARG; 1-10 0 muM), however, relaxation was significantly more reduced in femoral arter y rings from 2-week-old than from newborn, with lower pD(2) values in the o lder age group. Inhibition of large (BKCa) conductance calcium-sensitive K channels with tetraethylammonium chloride (TEA; 1 mM), gave a significant rightward shift in the concentration-response curves to ACh which was of th e same magnitude in both age groups. The ACh-induced vasodilation was aboli shed in both age groups by high K+ (20 mM) in combination with L-NOARG (100 muM). The relative increase in cGMP levels after addition of ACh (10 nM) w as significantly larger in rings from newborn compared with 2-week-old pigl ets (12- vs. four-fold). In summary, sensitivity to NOS inhibition increase d with age while the effect of K+ channel blockade with TEA was the same in femoral artery rings from newborn to 2-week-old piglets. Lower sensitivity to NOS inhibition and a larger increase in cGMP in response to ACh could i ndicate a higher efficacy of the NO/cGMP pathway in this vessel in the newb orn piglet.