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

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Abstract

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, acetyicholine (ACH) and substance P (SP). Methods: Arteries from mature foetal (5 days), neonatal (≈5 min), newborn (60-84 h) and adult pigs (≥6 months) were isolated, mounted for in vitro isometric force recording, activated with PGF2α (30 μmol/l) and relaxed with BYK (10 pmol/l-1 μmol/l), SP (10 pmol/l-0.1 μmol/l) or ACH (1 nmol/l-1 mmol/l). Results: (i) BYK: L-NAME (100 μmol/l) attenuated relaxations in foetal EPA (≈55%) but nearly abolished them in the adult (≈80%). In RPA, L-NAME nearly abolished (≈90%) relaxations in the foetus and this effect diminished progressively with age to ≈20% in the adult. Indomethacin (IND, μmol/l) attenuated relaxations in neonatal (≈25%), new-born and adult EPA (both ≈45%). Together, L-NAME and IND abolished relaxations in all EPA and in neonatal RPA but not in older RPA. SKF525a (100 μmol/l) attenuated relaxations in foetal RPA (≈4%), diminishing in the adult RPA to ≈10%. Together, SKF52Sa and L-NAME largely abolished relaxations in postnatal RPA (≈80%). Activation with K+=125 mmol/l attenuated relaxations in adult EPA (≈80%), foetal RPA (≈45%) and neonatal RPA (≈75%) and abolished relaxations in RPA from older ages. (ii) ACH: L-NAME abolished relaxations in new-born EPA and RPA. In adult EPA, combined L-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 (in 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 ACH, 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. © 2001 Elsevier Science B.V.

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Boels, P. J., Deutsch, J., Gao, B., & Haworth, S. G. (2001). Perinatal development influences mechanisms of bradykinin-induced relaxations in pulmonary resistance and conduit arteries differently. Cardiovascular Research, 51(1), 140–150. https://doi.org/10.1016/S0008-6363(01)00275-9

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