Hypoxic pulmonary vasodilation: A paradigm shift with a hydrogen sulfide mechanism

Kenneth R. Olson, Nathan L. Whitfield, Shawn E. Bearden, Judy St. Leger, Erika Nilson, Yan Gao, Jane A. Madden

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

Hypoxic pulmonary vasoconstriction (HVC), an intrinsic and assumed ubiquitous response of mammalian pulmonary blood vessels, matches regional ventilation to perfusion via an unknown O2-sensing mechanism. Global pulmonary hypoxia experienced by individuals suffering from chronic obstructive pulmonary disease or numerous hypoventilation syndromes, including sleep apnea, often produces maladaptive pulmonary hypertension, but pulmonary hypertension is not observed in diving mammals, where profound hypoxia is routine. Here we examined the response of cow and sea lion pulmonary arteries (PA) to hypoxia and observed the expected HVC in the former and a unique hypoxic vasodilation in resistance vessels in the latter. We then used this disparate response to examine the O2-sensing mechanism. In both animals, exogenous H 2S mimicked the vasoactive effects of hypoxia in isolated PA. H 2S-synthesizing enzymes, cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfur transferase, were identified in lung tissue from both animals by one-dimensional Western blot analysis and immunohistochemistry. The relationship between H2S production/consumption and O2 was examined in real time by use of amperometric H2S and O2 sensors. H2S was produced by sea lion and cow lung homogenate in the absence of O2, but it was rapidly consumed when O2 was present. Furthermore, consumption of exogenous H2S by cow lung homogenate, PA smooth muscle cells, and heart mitochondria was O2 dependent and exhibited maximal sensitivity at physiologically relevant PO2 levels. These studies show that HVC is not an intrinsic property of PA and provide further evidence for O 2-dependent H2S metabolism in O2 sensing.

Original languageEnglish (US)
Pages (from-to)R51-R60
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume298
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • Hypoxic vasoconstriction
  • Pinniped
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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