Adenosine-angiotensin II interactions. Part II. The role of adenosine in regulating angiotensin II-induced changes in heart rate and aldosterone release

BJ Holycross, P Li and EK Jackson

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.

The purpose of the present study was to determine whether endogenous adenosine (ADO) participates in angiotensin II (AII)-induced decreases in heart rate (HR) and regulates AII-induced aldosterone (ALDO) release. To test these hypotheses we investigated: 1) the effects of ADO and AII on base-line HR and ALDO levels; 2) the effects of ADO on AII-induced bradycardia and AII-induced increases in ALDO levels; 3) the effects of ADO receptor antagonists [caffeine and/or 1,3-dipropyl-8- p-sulfophenylxanthine (DPSPX)] on AII-induced bradycardia and AII- induced increases in ALDO levels; and 4) the effects of ADO receptor hypersensitivity on AII-induced bradycardia. In the latter experiments, the animals were rendered hypersensitive to the bradycardic effects of ADO by administering caffeine for 1 week then abruptly withdrawing caffeine 18 hr before the experiment, i.e., caffeine withdrawal. Intravenous infusions of either ADO or AII decreased base-line HR and ADO reduced the bradycardic response to AII. Intravenous infusions of DPSPX attenuated and caffeine withdrawal potentiated AII-induced bradycardia without modifying AII-induced increases in arterial blood pressure. AII increased and ADO did not alter base-line plasma ALDO levels; however, ADO attenuated by 50% AII-induced increases in ALDO levels. Neither DPSPX nor caffeine altered the ability of AII to increase plasma ALDO levels. These results indicate that although ADO has the potential to modulate AII-induced increases in plasma ALDO concentrations, endogenous ADO does not regulate the effects of AII on plasma ALDO levels under the conditions of these studies. However, endogenous ADO, in some way, contributes substantially to AII-induced bradycardia.

Volume 250, Issue 2, pp. 442-453, 08/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics