Contribution of endothelium and cardiomyocytes to hypoxia-induced adenosine release.

Abstract

The cellular source and role of adenosine in hypoxia-induced coronary vasodilatation was investigated. The endothelial adenine nucleotides of Langendorff-perfused rat hearts were prelabelled by perfusion with [3H]adenosine and the changes in specific radioactivities were employed to identify the source of the adenine compounds released. The contribution of ecto-5'-nucleotidase was evaluated in perfusions with the inhibitor alpha,beta-methylene adenosine diphosphate (AOPCP). Absorbance of the effluent perfusate at 260 nm was monitored continuously as a convenient means of detecting the output of total purines, and it showed a good correlation with HPLC-measured purines (r = 0.72, P < 0.001). Coronary flow increased sharply in hypoxia but tended to decrease after 2 min, while effluent radioactivity and absorbance increased steadily. The radioactivity-to-absorbance ratio and the specific radioactivity of chemically measured total purines began to increase after 3 min. The changes in effluent concentrations of adenosine and inosine were much more prominent than those in free purines. The specific radioactivity of adenosine decreased sharply at the onset of hypoxia which indicates that hypoxia affects mainly working cardiomyocytes. This also means that endothelial adenosine release is delayed if compared to coronary vasoregulation. Although the inhibition of ecto-5'-nucleotidase caused a decrease in the release of adenosine and adenine moiety label from the heart it is most likely that adenosine was mainly derived from intracellular sources, because the hypoxia-induced increase in the concentration of adenosine was more excessive than that of AMP. In addition, AOPCP decreased the basal work load and coronary flow of the heart, slightly attenuated the hypoxia-induced flow increase and prevented adenylate loss during hypoxia. Thus, the data emphasize the role of cardiomyocytes in adenosine production and coronary vasoregulation.

• Authors: M J Raatikainen, K J Peuhkurinen, I E Hassinen
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 26 Issue 8 Pg. 1069-80 (Aug 1994) ISSN: 0022-2828 [Print] England
• PMID: 7799447 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Muscle Proteins
• alpha,beta-methyleneadenosine 5'-diphosphate
• Uric Acid
• Adenosine Diphosphate
• 5'-Nucleotidase
• Adenosine

Topics

• 5'-Nucleotidase (physiology)
• Adenosine (metabolism)
• Adenosine Diphosphate (analogs & derivatives, pharmacology)
• Animals
• Cell Hypoxia
• Coronary Circulation
• Coronary Vessels (physiology)
• Endothelium, Vascular (physiology)
• Energy Metabolism
• Heart (physiology)
• Male
• Muscle Proteins (physiology)
• Myocardium (cytology, metabolism)
• Perfusion
• Rats
• Rats, Sprague-Dawley
• Uric Acid (analysis)
• Vasodilation