Vasoconstriction of intrapulmonary arteries to P2-receptor nucleotides in normal and pulmonary hypertensive newborn piglets

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Abstract
The vasoconstrictor responses of isolated intrapulmonary arteries (IPA) to P2‐receptor agonists was investigated during adaptation to extrauterine life in the normal piglet and the effect of pulmonary hypertension was studied following exposure of newborn animals to chronic hypobaric hypoxia (51 kPa) for 3 days. At resting tone, α,β‐methyleneATP (α,β‐meATP) (P2X‐receptor agonist) contracted intrapulmonary arteries from adult, but not immature pigs, and repeated application desensitized the response. Adenosine 5′‐triphosphate (ATP) induced endothelium‐independent relaxation at low concentrations at all ages, a variable contractile response to high concentrations developed by 3 days, becoming larger and consistent by 14 days of age. Uridine 5′‐triphosphate (UTP) evoked a contractile response in normal intrapulmonary arteries from foetal to adult life, the magnitude of the response increasing with age. Endothelial removal and pre‐incubation with Nω‐nitro‐L‐arginine methyl ester (L‐NAME) (100 μM) increased the contractile response of adult vessels. Pre‐incubation with α,β‐meATP (100 μM), increased the contractile response to UTP in both newborn and adult vessels. ATP‐induced relaxations were reduced in newborn vessels but there was no effect on the responses of adult vessels. Responses to UTP, ATP and α,β‐meATP of intrapulmonary arteries from newborn piglets exposed to chronic hypobaric hypoxia for 3 days were normal. In summary, UTP elicited marked vasoconstriction of porcine IPA at all ages. UTP and ATP responses were consistent with activation of the P2Y4‐receptor recently identified in vascular smooth muscle by others. α,β‐meATP induced a small vasoconstriction in the adult probably via the P2X1‐receptor. Responses remained normal in neonatal pulmonary hypertension. British Journal of Pharmacology (1999) 128, 549–555; doi:10.1038/sj.bjp.0702814

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