Studies on the Relative Effects of Prostaglandins, Bradykinin, 5‐hydroxytryptamine and Histamine on the Synovial Microcirculation in Dogs

Abstract

I The relative effects of prostaglandins E,, E2, Fla, F2a, bradykinin, histamine and 5-hydroxytryptamine (5-HT) on the canine synovial microcirculation were investigated using the rate of clearance ofradioactive xenon ("'Xe) as an index of synovial perfusion.2 All the compounds tested, except prostaglandin F1a, produced a vasodilator effect. The descending order of potency ofthe active compounds was (i) prostaglandin El, (ii) prostaglandin E2 and bradykinin, (iii) histamine and 5-HT, (iv) prostaglandin F2a. The most potent compound tested, prostaglandin El produced an effect in nanogram amounts in each joint. 3 Prostaglandin F2a has been reported to have an anti-inflammatory action; however no evidence was found of antagonism of prostaglandin E, by two dose levels of prostaglandin FM,. 4 Preliminary studies showed that threshold doses of prostaglandin E, did not potentiate the vasodilator action ofthreshold or sub-threshold doses of bradykinin in the dog synovium.

Mechanism of enhanced fibroblast arachidonic acid metabolism by mononuclear cell factor.

“…Chronic inflammation has been associated with elevated levels of PGE2 at the site of injury. PGE2 is a vasodilator (10), enhances vascular permeability (11), and plays a role in the regulation of the immune response by modulating T lymphocyte proliferation, macrophage cytotoxicity, and lymphokine production (12).…”

Actions of Locally Administered Adrenoceptor Agonists on Increased Plasma Protein Extravasation and Blood Flow in Guinea‐pig Skin

“…The log of the ratio C,/C0 was plotted against time and the half-life (T1/2 min) of clearance of the gas was obtained by interpolation (or by extrapolation in a few instances). A decrease in T1/2 was taken to denote vasodilatation and an increase to denote vasoconstriction as described by Dick, Grennan & Zeitlin (1976). Each drug, or drug combination, was tested in at least 3 animals.…”

THE EFFECTS OF PROSTAGLANDIN E1, BRADYKININ AND HISTAMINE ON CANINE SYNOVIAL VASCULAR PERMEABILITY

“…Prostaglandin E1 has been shown to potentiate the rat paw oedema produced by bradykinin (Moncada, Ferreira & Vane, 1973;Lewis, Nelson & Sugrue, 1975) and to potentiate the actions of bradykinin and histamine in increasing cutaneous vascular permeability in guinea-pigs (Williams & Morley, 1973). No such potentiation was found in our earlier studies on dog synovial blood flow (Dick et al, 1976).…”

“…We have previously shown that normal synovial blood flow is extremely sensitive to the vasodilator effects of prostaglandin E1 and bradykinin, and reactive but to a lesser degree, to histamine (Dick, Grennan & Zeitlin, 1976).…”