Interaction of carbon monoxide and adenosine in the nucleus tractus solitarii of rats.
Carbon monoxide has been identified as an endogenous biological messenger in the brain. Heme oxygenase catalyzes the metabolism of heme to carbon monoxide and biliverdin. Previously, we have shown the involvement of carbon monoxide in central cardiovascular regulation, baroreflex modulation, and glutamatergic neurotransmission in the nucleus tractus solitarii of rats. We also showed that adenosine increased the release of glutamate in the nucleus tractus solitarii. In this study, we investigated the possible interactions of carbon monoxide and adenosine in the nucleus tractus solitarii. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure were monitored intra-arterially. Unilateral microinjection of increasing doses of hemin (0.01 to 3.3 nmol), a heme molecule cleaved by heme oxygenase to yield carbon monoxide, produced a significant decrease in blood pressure and heart rate in a dose-dependent manner. In addition, similar cardiovascular effects were observed after injection of adenosine (2.3 nmol). These cardiovascular effects of hemin were attenuated by prior administration of the adenosine receptor antagonist 1,3-dipropyl-8-sulfophenylxanthine. Similarly, pretreatment of the heme oxygenase inhibitor zinc protoporphyrin IX or zinc deuteroporphyrin 2,4-bis glycol also attenuated the depressor and bradycardic effects of adenosine. These results indicate that the interaction between carbon monoxide and adenosine may contribute to the activation of heme oxygenase in central cardiovascular regulation.
Lin
Chia-Hui
CH
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386-Ta-Chung 1st Rd, Kaohsiung, Taiwan, ROC.
Lo
Wan-Chen
WC
Hsiao
Michael
M
Tseng
Ching-Jiunn
CJ
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002248:Carbon Monoxide / Q000378:metabolism*; D003905:Deuteroporphyrins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors; D006427:Hemin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D011524:Protoporphyrins / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
D003905:Deuteroporphyrins; D011524:Protoporphyrins; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); C017803:zinc protoporphyrin; D006427:Hemin; D002248:Carbon Monoxide; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D006419:Heme Oxygenase (Decyclizing); D000241:Adenosine