Abrogation of alpha-adrenergic vasoactivity in chronically inflamed rat knee joints.
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 alpha-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 alpha(1)-adrenoceptor agonists methoxamine and phenylephrine and the alpha(2)-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 alpha(2)-adrenergic effects > alpha(1)-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 alpha(2)-adrenoceptors. Chronic joint inflammation compromises alpha(1)- and alpha(2)-adrenoceptor function, and this change in alpha-adrenergic responsiveness may help explain the perfusion changes commonly associated with inflammatory arthritis.
McDougall
J J
JJ
McCaig Centre for Joint Injury & Arthritis Research, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada. mcdougaj@ucalgary.ca
D000287:Administration, Topical; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology; D002908:Chronic Disease; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005620:Freund's Adjuvant; D006614:Hindlimb; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D017746:Joint Capsule / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D010656:Phenylephrine; D005620:Freund's Adjuvant; D008729:Methoxamine; D003000:Clonidine