Perinatal development influences mechanisms of bradykinin-induced relaxations in pulmonary resistance and conduit arteries differently

Objective: As bradykinin (BYK) relaxes conduit (EPA) and resistance (RPA) p ulmonary arteries from both perinatal and adult lungs, we investigated whet her this vasodilator's relaxation-mechanisms were altered during perinatal development, differed between EPA and RPA and differed with other endotheli um-dependent vasodilators. acetylcholine (ACH) and substance P (SP). Method s: Arteries from mature foetal (5 days), neonatal(approximate to5 min), new born (60-84 h) and adult pigs (greater than or equal to6 months) were isola ted. mounted for in vitro isometric force recording, activated with PGF(2 a lpha) (30 mu mol/l) and relaxed with BYK (10 pmol/l-l mu mol/l), SP (10 pmo l/l-0.1 mu mol/l) or ACH (1 nmol/l-l mmol/l). Results: (i)BYK: L-NAME (100 mu mol/l) attenuated relaxations in foetal EPA (approximate to 55%) but nea rly abolished them in the adult (approximate to 80%). In RPA, L-NAME nearly abolished (approximate to 90%) relaxations in the foetus and this effect d iminished progressively with age to approximate to 20% in the adult. Indome thacin (IND, mu mol/l) attenuated relaxations in neonatal (approximate to 2 5%). new-born and adult EPA (both approximate to 45%). Together, L-NAME and IND abolished relaxations in all EPA and in neonatal RPA but not in older RPA. SKF525a (100 mu mol/l) attenuated relaxations in foetal RPA (approxima te to4%). diminishing in the adult RPA to approximate to 10%. Together. SKF 52Sa and L-NAME largely abolished relaxations in postnatal RPA (approximate to 80%). Activation with K+ = 125 mmol/l attenuated relaxations in adult E PA (approximate to 80%), foetal RPA (approximate to 45%) and neonatal RPA ( approximate to 75%) and abolished relaxations in RPA from older ages. (ii) AGH: L-NAME abolished relaxations in new-born EPA and RPA. In adult EPA, co mbined I.-NAME and IND moderately attenuated relaxations. (iii) SP: Combine d application of L-NAME and IND attenuated relaxations to a similar degree in new-born and adult EPA and RPA. Conclusions: In postnatal EPA, BYK-relax ations depend completely on prostaglandin- and NO-synthesis whereas those t o SP (at all ages) and ACH tin the adult) do not. In RPA, BYK-relaxations d evelop from being completely dependant on the sole release of NO (foetus) t o being almost completely independent of it (adult). a situation mimicked p artially by SP but not by AGH. which, in new-born RPA is completely depende nt on NO. BYK-relaxations in postnatal RPA depend on the release of a hyper polarising factor generated through an SKF525a-sensitive pathway in conjunc tion with NO. The mechanisms of endothelium-dependent BYK-relaxations in th e pulmonary vascular bed undergo diverging alterations. depending on the st age of development and arterial size/function. These changes are specific f or BYK as they differ from those obtained from ACH or SP. (C) 2001 Elsevier Science B.V. All rights reserved.