Induction of heme oxygenase-1 is involved in carbon monoxide-mediated central cardiovascular regulation

Wan-Chen Lo1, Pei-Jung Lu, Wen-Yu Ho

  • 1Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung, Taiwan.

Insights

Carbon monoxide (CO) is a brain messenger. Heme oxygenase-1 (HO-1) induction in the nucleus tractus solitarii after hemin injection suggests HO-1 generates CO, influencing cardiovascular control.

Area of Science:

  • Neuroscience
  • Cardiovascular Physiology
  • Biochemistry

Background:

  • Carbon monoxide (CO) acts as an endogenous biological messenger in the brain.
  • Heme oxygenase (HO) enzymes metabolize heme, producing CO.
  • Previous research implicated CO in central cardiovascular regulation within the nucleus tractus solitarii (NTS).

Purpose of the Study:

  • To identify which heme oxygenase (HO) isoform is induced by hemin in the NTS.
  • To determine the in situ distribution of induced HO isoforms within the NTS.
  • To investigate the role of HO-1 in the cardiovascular effects of hemin in the NTS.

Main Methods:

  • Male Sprague-Dawley rats were anesthetized and instrumented for intra-arterial blood pressure monitoring.
  • Unilateral microinjections of hemin (1 nmol) or the HO inhibitor zinc protoporphyrin IX (ZnPPIX) were administered into the NTS.
  • HO-1 and HO-2 protein expression and cellular localization in the NTS were analyzed in situ post-injection.

Main Results:

  • Hemin microinjection into the NTS significantly decreased blood pressure and heart rate.
  • These cardiovascular effects were attenuated by prior ZnPPIX administration.
  • Hemin injection induced HO-1 protein expression in glial cells and neurons within the NTS, an effect inhibited by ZnPPIX.
  • No significant changes in HO-2 expression were observed.

Conclusions:

  • Heme oxygenase-1 (HO-1), not HO-2, is induced in the NTS following hemin administration.
  • HO-1 is likely responsible for the generation of CO in the NTS.
  • The HO-1-derived CO contributes to the central regulation of cardiovascular function.

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