Vascular impairment of adenosinergic system in hypertension: increased adenosine bioavailability and differential distribution of adenosine receptors and nucleoside transporters.

Abstract

Adenosinergic system regulates vascular tonicity through the complex system of adenosine, adenosine receptors (ARs) and nucleoside transporters. This work aimed at evaluating the impact of hypertension on adenosine bioavailability and expression/distribution profile of AR subtypes (A1, A2A, A2B, A3) and equilibrative nucleoside transporters (ENT1, ENT2, ENT3, ENT4). Adenosine wasmeasured in vascular tissue extracts by HPLC (fluorescence detection); immunoreactivities (ARs/ENTs) in mesenteric arteries/veins from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were analyzedby histomorphometry. Significantly higher adenosine bioavailability occurred in arteries than in veins. Adenosine bioavailability was even more increased in SHR vessels. Expression/distribution of ARs and ENTs observed in all vascular layers (intima, media, adventitia), with more intensified expression in arteries than in veins. In SHR arteries, a downregulation of all ENT along with downregulated and punctuated distribution of A1 and A2B receptors occurred comparatively to WKY arteries. By contrast, expressions of ARs and ENTs were unaltered, exception for an A2A receptor upregulation, and ENT2 downregulation in SHR veins relatively to WKY veins. Our data evidenced clear alterations of adenosinergic dynamics occurring in hypertension, particularly in arterial vessels. An increased adenosine bioavailability was observed, for the first time, in hypertensive vascular tissues.