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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on March 24, 2006; DOI: 10.1124/jpet.105.099051

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*CARBON MONOXIDE


Received for publication November 30, 2005.
Revised March 23, 2006.
Accepted for publication March 23, 2006.

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

Wan-Chen Lo 1, Pei-Jung Lu 1, Wen-Yu Ho 1, Michael Hsiao 2, Ching-Jiunn Tseng 1*

1 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 2 Genomics Research Center, Academia Sinica, Taipei, Taiwan

* Address correspondence to: E-mail: cjtseng{at}isca.vghks.gov.tw

Abstract

Carbon monoxide (CO) has been identified as an endogenous biological messenger in the brain. Heme oxygenase (HO) catalyzes the metabolism of heme to CO and biliverdin. Previously, we have shown the involvement of CO in central cardiovascular regulation, baroreflex modulation, and glutaminergic neurotransmission in the nucleus tractus solitarii (NTS) of rats. In this study, we examined which HO isoform could be induced after hemin injection in the NTS. We also investigated their in-situ distributions in the NTS after induction. Male Sprague-Dawley (SD) rats were anesthetized with urethane, and blood pressure was monitored intra-arterially. Unilateral microinjection of hemin (1 nmol), a heme molecule cleaved by HO to yield CO, produced significant decrease in blood pressure and heart rate. These cardiovascular effects of hemin were attenuated by prior administration of HO inhibitor zinc protoporphyrin IX (ZnPPIX). Microinjection of hemin into NTS resulted in significant induction of HO-1 protein expression in-situ. Pretreatment of ZnPPIX significantly inhibited the HO-1 induction after hemin injection. No significant changes of HO-2 expressions were found after hemin injection and ZnPPIX pretreatment. The in-situ inductions of the HO-1 protein expression were further confirmed to be in glial cells and neurons after hemin injections into the NTS. These results indicated HO-1 but not HO-2 might be responsible for the generation of CO and contribute to central control of cardiovascular effects.


Key words: HO-1, HO-2, blood pressure, carbon monoxide, central cardiovascular regulation, nucleus tractus solitarii


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