Influence of prostaglandin-synthesis inhibitors on carbachol- and histamine-induced vasodilatation in perfused rat hindquarters.

In perfused rat hindquarters, in which vascular tone was maintained by norepinephrine, carbachol-induced dilatations were blocked by atropine (10(-7) M), while histamine dilatations were inhibited as well by mepyramine (10(-6) M) as by cimetidine (10(-5) M) indicating a histamine effect through both H1- and H2-receptors. This double-receptor histamine effect was confirmed by the observation that specific H1- and H2-receptor agonists, respectively PEA (2-pyridyl-ethyl-aminedihydrochloride) and dimaprit also produced a vasodilatation. Carbachol- and histamine-induced dilatations were also inhibited by ETYA (5,8,11,14-eicosatetraynoic acid) and quinacrine but not by indomethacin. The inhibition of the histamine vasodilatation appeared to rest on an interference with the H1-receptor mechanism. It is concluded that metabolites of arachidonic acid possibly mediate the dilating effect of carbachol, acting through muscarine receptors, and of histamine, acting through H1-receptors.