Histamine receptors in the synovial microcirculation.

This study was designed to investigate the respective roles of H(1) and H(2) receptors in the control of the microcirculation by examining the effectiveness of the H(2) receptor antagonist metiamide (Met.) and H(1) receptor antagonist mepyramine is blocking the action of histamine on synovial perfusion. Synovial perfusion was monitored indirectly by calculating the half-life (T1/2 min.) of the clearance rate of 133-Xe from canine diarthrodial joints. The 133-Xe clearance rate, unaffected by metiamide alone, was consistently increased by histamine alone. Metiamide produced a dose related effect on the histamine response with consistent abolition of response at high dose ratios of metiamide to histamine variable response at intermediate and a pronounced histamine response at low dose ratios. Mepyramine produced no such antagonism of the histamine response and in certain doses, by itself caused an increase in 133-Xe clearance rate. This effect of mepyramine was thought to be related to its histamine releasing properties a view supported by the reduction in this vasodilator response following certain doses of metiamide. The response of the 133-Xe clearance rate to histamine returned approximately one hour after treatment with metiamide (500 mug) and metiamide did not antagonise the effects of alpha and beta adrenergic agents on the 133-Xe clearance rate. Thus, this study has provided evidence for the presence of H(2) but not H(1) receptors in the synovial microcirculation.