Pharmacology of the Adenosine A(3) 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 A(3) receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A(3) 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 A(3) receptor mediated coronary vasodilation in the rat heart. RESULTS: Adenosine A(3) receptor agonists induced coronary vasodilation. The expression of adenosine A(3) receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A(3) receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A(3) receptor agonists. CONCLUSIONS: This study demonstrated alterations in the expression of adenosine A(3) receptors occurred in a tissue specific mode, and reduced adenosine A(3) receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A(3) receptor in hypertensive hearts suggest that adenosine A(3) 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 A(3) receptor agonists.