DEVELOPMENTAL-CHANGES IN ENDOTHELIUM-DEPENDENT PULMONARY VASODILATATION IN PIGS

1 We compared in vitro endothelium-dependent vasorelaxant responses to acetylcholine (ACh) and the endothelium-independent vasodilator response to sodium nitroprusside (SNP) in prostaglandin F2-alpha (PGF2-alpha)-precontracted muscular pulmonary arteries (PA) from pigs aged 5 min to 2 h (neonatal), 3-10 days, 3-8 weeks and adults. 2 In the pulmonary artery (PA) rings from neonatal animals, the vasodilator response to ACh was negligible. However, responses to ACh were present in all PA rings from older animals, being greatest at 3-10 days and then decreasing with age (P < 0.001, ANOVA). ACh (30-mu-M) induced a 1 +/- 1%, 92 +/- 9%, 62 +/- 5% and 51 +/- 6% reduction of the PGF2-alpha-generated tension in neonatal, 3-10 days, 3-8 weeks and adult groups, respectively. 3 The relaxant response to SNP was present in the PA rings from all age groups and increased with age (P < 0.001, ANOVA). SNP (1-mu-M)-induced relaxation was 55 +/- 9%, 73 +/- 7%, 97 +/- 5% and 93 +/- 6% in neonatal, 3-10 days, 3-8 week and adult groups, respectively. 4 Removal of the vascular endothelium abolished the relaxant response to ACh but had no effect on the response to SNP in any groups. 5 N(G)-monomethyl-L-arginine (30-mu-M), a nitric oxide synthesis inhibitor, inhibited the response to ACh but not to SNP. The lipoxygenase inhibitor, nordihydroguaiaretic acid, had no significant effect on responses to ACh or SNP in any group. 6 These findings suggest that the nitric oxide pathway may not play a part in dilating the pig pulmonary arteries at birth, but may be important during the transitional period of establishing a stable post-natal pulmonary circulation. The increase in response to SNP with age parallels the increase in smooth muscle cell myofilaments to which it may be related.