Paracrine purinergic signaling determines lung endothelial nitric oxide production

Rainer Kiefmann, Mohammad N. Islam, Jens Lindert, Kaushik Parthasarathi, Jahar Bhattacharya

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Although the vascular bed is a major source of nitric oxide (NO) production, factors regulating the production remain unclear. We considered the role played by paracrine signaling. Determinations by fluorescence microscopy in isolated, blood-perfused rat and mouse lungs revealed that a brief lung expansion enhanced cytosolic Ca2+ (Ca2+cyt) oscillations in alveolar epithelial (AEC) and endothelial (EC) cells, and NO production in EC. Furthermore, as assessed by a novel microlavage assay, alveolar ATP production increased. Intra-alveolar microinfusion of the purinergic receptor antagonist, PPADS, and the nucleotide hydrolyzing enzyme, apyrase, each completely blocked the Ca2+cyt and NO responses in EC. Lung expansion induced Ca2+cyt oscillations in mice lacking the P2Y1, but not the P2Y2, purinergic receptors, which were located in the perivascular interstitium basolateral to AEC. Prolonged lung expansion instituted by mechanical ventilation at high tidal volume increased EC expression of nitrotyrosine, indicating development of nitrosative stress in lung microvessels. These findings reveal a novel mechanism in which mechanically induced purinergic signaling couples cross-compartmental Ca2+cyt oscillations to microvascular NO production.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number6
DOIs
StatePublished - Jun 1 2009

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Paracrine Communication
Nitric Oxide
Lung
Purinergic Antagonists
Purinergic P2Y2 Receptors
Apyrase
Tidal Volume
Microvessels
Fluorescence Microscopy
Artificial Respiration
Blood Vessels
Nucleotides
Endothelial Cells
Adenosine Triphosphate
Enzymes

All Science Journal Classification (ASJC) codes

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

Cite this

Paracrine purinergic signaling determines lung endothelial nitric oxide production. / Kiefmann, Rainer; Islam, Mohammad N.; Lindert, Jens; Parthasarathi, Kaushik; Bhattacharya, Jahar.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 296, No. 6, 01.06.2009.

Research output: Contribution to journalArticle

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