Increasing sympathetic nerve terminal-dependent plasma extravasation correlates with decreased arthritic joint injury in rats.
This study compared the pharmacology of adrenergic agents that influence plasma extravasation in normal animals with those agents that influence tissue injury in an inflammatory disease model. Specifically we studied the effects of beta 2- and alpha 2-adrenergic receptor agonists and antagonists on bradykinin-induced plasma extravasation in normal Sprague-Dawley rats and on joint injury in rats with experimental arthritis. Plasma extravasation induced by infusion of bradykinin in the rat knee joint was attenuated by the beta 2-agonist salbutamol or by the alpha 2-antagonist yohimbine, and was enhanced by the beta 2-antagonist, ICI-118,551, or by the alpha 2-agonist, clonidine. In rats that had undergone chemical symphathectomy, bradykinin-induced plasma extravasation was markedly reduced, and there was no enhancement of bradykinin-induced plasma extravasation by either ICI-118,551 or clonidine. Although ICI-118,551 and clonidine enhanced bradykinin-induced plasma extravasation, these drugs significantly reduced joint injury in rats with adjuvant-induced arthritis. Neither salbutamol nor yohimbine, however, significantly increased joint injury in the arthritic rats, presumably because arthritis severity is already high in these animals. Consistent with this hypothesis, both salbutamol and yohimbine did significantly increase the joint injury associated with experimental arthritis in Wistar-Kyoto rats, a strain which develops a mild adjuvant arthritis. The fact that increased plasma extravasation is associated with decreased arthritis severity suggests that plasma extravasation, a major sign of acute inflammation, contributes to tissue reparative processes.
Coderre
T J
TJ
Department of Anatomy, University of California, San Francisco 94143.
Chan
A K
AK
Helms
C
C
Basbaum
A I
AI
Levine
J D
JD
D000818:Animals; D001168:Arthritis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007270:Injections, Intra-Articular; D008297:Male; D009411:Nerve Endings / Q000502:physiology*; D010949:Plasma / Q000378:metabolism*; D011859:Radiography; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology
D013566:Sympathomimetics; D001920:Bradykinin