Abrogation of α-adrenergic vasoactivity in chronically inflamed rat knee joints

Abstract

It has previously been shown that chronic inflammation causes a reduction in sympathetic nerve-mediated vasoconstriction in rat knees. To determine whether this phenomenon is due to an alteration in smooth muscle adrenoceptor function, the present study compared the α-adrenoceptor profile of blood vessels supplying the anteromedial capsule of normal and chronically inflamed rat knee joints. While the rats were under urethan anesthesia, the α1-adrenoceptor agonists methoxamine and phenylephrine and the α2-adrenoceptor agonist clonidine (0.1-ml bolus; dose range 10−12-10−7 mol) were applied to exposed normal rat knees, resulting in a dose-dependent fall in capsular perfusion. Comparison of drug potencies indicated that α2-adrenergic effects > α1-vasoactivity. One week after intra-articular injection of Freund's complete adjuvant to induce chronic joint inflammation, the vasoconstrictor effects of methoxamine, phenylephrine, and clonidine were all significantly attenuated compared with normal controls. These findings show that the preponderance of sympathetic adrenergic vasoconstriction in the anteromedial capsule of the rat is carried out by postjunctional α2-adrenoceptors. Chronic joint inflammation compromises α1- and α2-adrenoceptor function, and this change in α-adrenergic responsiveness may help explain the perfusion changes commonly associated with inflammatory arthritis.