Cholinergic vasoregulation in normal and adjuvant monoarthritic rat knee joints.
The role of cholinergic nerves in joint vasomotor control was investigated in normal and chronically inflamed rat knees. Joint inflammation was induced by unilateral intraarticular injection of Freund's complete adjuvant and experiments were performed on both the ipsilateral and contralateral joints one and three weeks after treatment. Blood flow measurements of the exposed joints were obtained using a laser Doppler perfusion imager which provides relative changes in tissue perfusion. One week after adjuvant induction, basal perfusion in both ipsilateral and contralateral joints was significantly reduced compared to normal. At three weeks, ipsilateral knee perfusion had returned to normal, however, contralateral blood flow showed no such sign of recovery. Topical application of the muscarinic receptor antagonist atropine caused a fall in knee joint basal perfusion suggesting that cholinergic nerves are inherently involved in the physiological control of rat knee blood vessels. Acetylcholine chloride (10(-13)-10(-8) mol) in normal rats produced a dose-dependent vasodilatation of the articular microvasculature with the highest dose causing blood flow to increase by about 85%. This dilator response was attenuated in the ipsilateral monoarthritic joint at both one and three weeks post-injection while contralateral joints showed a normal response to acetylcholine at both of the time points tested. This study implicates cholinergic nerves in rat knee joint vasoregulation, however, the impairment of this mechanism by chronic inflammation could exacerbate the disease process by starving the joint of much needed vascular nourishment. Furthermore, the preservation of cholinergic responses in the contralateral knee despite a fall in basal perfusion suggests that alternative non-cholinergic mechanisms may be responsible for the hypoaemia in this joint.
McCaig Centre for Joint Injury and Arthritis Research, Department of Surgery, University of Calgary, Alberta, Canada. mcdougaj@acs.ucalgary.ca
J J
JJ
McDougall
R D
RD
Elenko
R C
RC
Bray
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000502:physiology*; D007719:Knee Joint / Q000098:blood supply*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology*
D010276:Parasympatholytics; D014665:Vasodilator Agents; D001285:Atropine; D000109:Acetylcholine