Induction of Heme Oxygenase-1 Is Involved in Carbon Monoxide-Mediated Central Cardiovascular Regulation
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (W.-C.L., P.-J.L., W.-Y.H., C.-J.T.); and Genomics Research Center, Academia Sinica, Taipei, Taiwan (M.H.)
- Address correspondence to:
Dr. Ching-Jiunn Tseng, Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung, Taiwan. 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 neuro-transmission 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 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 expression 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.
Footnotes
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This work was supported by National Science Council Grant NSC93-2320-B075B-003 and by Kaohsiung Veterans General Hospital Grant VGHKS93-17 (to C.-J.T.).
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.105.099051.
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ABBREVIATIONS: HO, heme oxygenase; CO, carbon monoxide; NO, nitric oxide; NTS, nucleus tractus solitarii; ZnPPIX, zinc protoporphyrin IX; BP, blood pressure; HR, heart rate; bpm, beat(s) per minute; GFAP, anti-glial fibrillary acidic protein; NeuN, neuronal nuclei; RT, reverse transcription; PCR, polymerase chain reaction; SD, Sprague-Dawley.
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- Received November 29, 2005.
- Accepted March 23, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
