Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

• Published in: PloS one Vol. 11; no. 2; p. e0150021
• Main Authors: Ho, Ming-Fen, Low, Leanne M, Rose'Meyer, Roselyn B
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2016; Public Library of Science (PLoS)
• Subjects: Adenosine; Adenosine A3 Receptor Agonists - pharmacology; Adenosine A3 receptors; Animal tissues; Animals; Biology and Life Sciences; Blood; Blood vessels; Coronary vessels; Coronary Vessels - drug effects; Coronary Vessels - physiopathology; Down-regulation; Essential Hypertension; Gene Expression Regulation - drug effects; Heart; Heart - drug effects; Heart - physiopathology; Hypertension; Hypertension - genetics; Hypertension - metabolism; Hypertension - physiopathology; Kinases; Male; Medicine and Health Sciences; mRNA; Organ Specificity; Perfusion; Pharmacology; Rats; Receptor, Adenosine A3 - genetics; Receptor, Adenosine A3 - metabolism; Receptors; Research and Analysis Methods; Rodents; Signal transduction; Signaling; Tissues; Vasodilation; Vasodilation - drug effects; Queensland Australia; Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0150021

Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation.
mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart.
Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists.
This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists.