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

Background

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.

Methods

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.

Results

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.

Conclusions

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.