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) pulmonary arteries from both perinatal and adult lungs, we investigated whether this vasodilator's relaxation-mechanisms were altered during perinatal development, differed between EPA and RPA and differed with other endothelium-dependent vasodilators. acetylcholine (ACH) and substance P (SP). Methods: Arteries from mature foetal (5 days), neonatal(approximate to5 min), newborn (60-84 h) and adult pigs (greater than or equal to6 months) were isolated. mounted for in vitro isometric force recording, activated with PGF(2 alpha) (30 mu mol/l) and relaxed with BYK (10 pmol/l-l mu mol/l), SP (10 pmol/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 nearly abolished them in the adult (approximate to 80%). In RPA, L-NAME nearly abolished (approximate to 90%) relaxations in the foetus and this effect diminished progressively with age to approximate to 20% in the adult. Indomethacin (IND, mu mol/l) attenuated relaxations in neonatal (approximate to 25%). 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 (approximate to4%). diminishing in the adult RPA to approximate to 10%. Together. SKF52Sa and L-NAME largely abolished relaxations in postnatal RPA (approximate to 80%). Activation with K+ = 125 mmol/l attenuated relaxations in adult EPA (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, combined I.-NAME and IND moderately attenuated relaxations. (iii) SP: Combined 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-relaxations depend completely on prostaglandin- and NO-synthesis whereas those to SP (at all ages) and ACH tin the adult) do not. In RPA, BYK-relaxations develop from being completely dependant on the sole release of NO (foetus) to being almost completely independent of it (adult). a situation mimicked partially by SP but not by AGH. which, in new-born RPA is completely dependent on NO. BYK-relaxations in postnatal RPA depend on the release of a hyperpolarising factor generated through an SKF525a-sensitive pathway in conjunction with NO. The mechanisms of endothelium-dependent BYK-relaxations in the pulmonary vascular bed undergo diverging alterations. depending on the stage of development and arterial size/function. These changes are specific for BYK as they differ from those obtained from ACH or SP. (C) 2001 Elsevier Science B.V. All rights reserved.