Effects of chronic treatment affecting heart rate on A1 adenosine receptor levels and their functions were studied. Treatment of rats with isoproterenol for 10 days accelerated heart rate and increased the level of adenosine receptors, in both the atria and ventricles. Negative dromotropic response of isolated heart to adenosine was enhanced in isoproterenol-treated rats. Similar results were obtained following treatment with atropine sulfate, or swimming training but not after treatment with thyroxine. On the other hand, treatment with amiodarone, which normally causes a decrease in heart rate, also increased the level of adenosine receptors in both atria and ventricles. The sensitivity of the isolated heart to the negative dromotropic and chronotropic effects of adenosine was not enhanced in the amiodarone treated rats. Similar results were obtained following treatment with propranolol, while treatment with PTU (6-n-propyl-2-thiouracil) increased adenosine sensitivity in the isolated heart. It was concluded that the levels of A1 adenosine receptors in the heart correspond to heart rate, and to cardiac efficiency. While an increase in heart rate was followed by up-regulation of A1 adenosine receptors, a decrease in heart rate caused a moderate elevation of these receptors.
Bibliographical noteFunding Information:
This study was supported in part by Grant no. 4390 from the Chief S cientist’s office of the Ministry of Health, Israel, and the Research Authority of Bar-Ilan University. Thanks to Ms. S. Victor for preparing this manuscript. We hereby declare that all procedures were performed according to the ‘Guiding Principles in the Care and Use of Animals’ of the American Physiological Society and in compliance with the laws of Israel.
- 8-cyclopentyl 1,3-dipropylxanthine
- Heart rate
- Ligand binding