Mechanisms of bradykinin-mediated dilation in newborn piglet pulmonary conducting and resistance vessels

Judy L. Aschner, Thuy K. Smith, Nora Kovacs, Joaquim M.B. Pinheiro, Mamta Fuloria

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Bradykinin (BK) is a potent dilator of the perinatal pulmonary circulation. We investigated segmental differences in BK-induced dilation in newborn pig large conducting pulmonary artery and vein rings and in pressurized pulmonary resistance arteries (PRA). In conducting pulmonary arteries and veins, BK-induced relaxation is abolished by endothelial disruption and by inhibition of nitric oxide (NO) synthase with nitro-L-arginine (L-NA). In PRA, two-thirds of the dilation response is L-NA insensitive. Charybdotoxin plus apamin and depolarization with KCl abolish the L-NA-insensitive dilations, findings that implicate the release of endothelium-derived hyperpolarizing factor (EDHF). However, endothelium-disrupted PRA retain the ability to dilate to BK but not to ACh or A-23187. In endothelium-disrupted PRA, dilation was inhibited by charybdotoxin. Thus in PRA, BK elicits dilation by multiple and duplicative signaling pathways. Release of NO and EDHF contributes to the response in endothelium-intact PRA; in endothelium-disrupted PRA, dilation occurs by direct activation of vascular smooth muscle calcium-dependent potassium channels. Redundant signaling pathways mediating pulmonary dilation to BK may be required to assure a smooth transition to extrauterine life.

Original languageEnglish (US)
Pages (from-to)L373-L382
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number2 27-2
Publication statusPublished - Aug 3 2002

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Keywords

  • Calcium-dependent potassium channels
  • Endothelium
  • Endothelium-derived hyperpolarizing factor
  • Nitric oxide
  • Pulmonary resistance arteries

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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