Changes in vascular porosity and joint blood flow during development of collagen induced arthritis in the rat. Modulation by indomethacin and L-NAME.
OBJECTIVE
To investigate changes in regional blood flows (RBF) and vascular porosity during the early phase of the autologous collagen II induced arthritis model (CIA) in rats and the possible influence of indomethacin and nitric oxide (NO) synthase on these variables.


METHODS
RBF was measured with the microsphere method and vascular porosity by determination of extravasation of radiolabeled albumin.


RESULTS
Onset of arthritis was associated with a rapid increase in vascular porosity in the knee. In ankles and paws this increase was somewhat slower in onset, but progressed during the course of the study. Acute treatment with indomethacin reduced albumin extravasation in the knees, but had no effect in the ankles or paws. Similarly, chronic indomethacin treatment also had no effect on the arthritic score. Serum levels of nitrite/nitrate did not change markedly during the development of CIA, and NO synthase inhibition did not affect the vascular porosity. The changes in RBF were relatively modest. In most tissues the total RBF increased with increasing tissue weight. Pretreatment with indomethacin reduced RBF in the paws, but not in the periarticular tissue.


CONCLUSIONS
The development of CIA is characterized by a marked rise in vascular porosity in affected joints, but the changes in RBF are much smaller and nonpersistent. The leakiness seems to be insensitive to the modulation of RBF and the responses in the knee show different characteristics compared to those in the ankle/paw.
Andersson
S E
SE
Department of Pharmacology, Astra-Draco AB, Lund, Sweden.
Ekström
G M
GM
D000818:Animals; D001168:Arthritis / Q000209:etiology / Q000503:physiopathology*; D002199:Capillary Permeability; D003094:Collagen; D004195:Disease Models, Animal; D005260:Female; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000097:blood; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D012039:Regional Blood Flow
D009573:Nitrites; D011453:Prostaglandins; D009569:Nitric Oxide; D003094:Collagen; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin