Maturational changes of endothelial vasoactive factors and pulmonary vascular tone at birth

The aim of this study was to determine which endothelial factors were invol ved in the decrease of pulmonary vascular resistance at birth, and how they changed with maturation. Response of intrapulmonary artery rings precontracted with prostaglandin F- 2 alpha, were studied from piglets aged <2 h, 2-3 day, 10 day and adult pig s for pharmacological responses to acetylcholine (ACh) and cromakalim (CMK) in the presence and the absence of the nitric oxide synthase (NOS) inhibit or, N-omega-nitro-L-arginine (LNA), the adenosine triphosphate sensitive po tassium (KATP) channel blocker, glibenclamide and the endothelin (ET)-A rec eptor antagonist, BQ123, In situ hybridization and immunochemistry studies were performed in lung tissues of the same animals in order to determine th e expression of NOS and ET. There was a small contractile effect of ACh in the newborn. Relaxation to A Ch, which was blocked by L-NA and reduced by glibenclamide, only appeared f rom the age of 3 days. The significantly greater relaxation to CMK in rings without endothelium (p<0.05) was abolished by BQ123 in the newborn, and th en disappeared by 2 days of age. Glibenclamide had a greater inhibitory eff ect on relaxation induced by CMK at 10 days than in the newborn and 2 days old piglets. NOS expression was low in pulmonary arteries of the newborn an d increased by 2 days of age whereas the converse was seen)with ET expressi on. It is concluded that: 1) relaxant response to acetylcholine was absent at b irth and appeared at 2 days; 2) the reduced relaxant response to cromakalin in rings with endothelium at birth could be blocked by BQ123; and 3) the e xpression of endothelin decreased whereas the expression of nitric oxide sy nthase increased from birth to 2 days of age.