Adrenergic Stimuli

In isolated rat spleen perfused with Tyrode's solution, prostaglandin (PG) Ei and E2, 0.2-2.5 ng/ml, reduced the vasoconstrictor responses to sympathetic nerve stimulation by 38-89% and 35-73% and to injected norepinephrine by 18-53% and 18-34%, respectively. In contrast, PGF2o and thromboxane B2 (TXB2) produced vasoconstriction and potentiated the vascular responses to both adrenergic stimuli, whereas PGD2 had variable effects. Stimulation of adrenergic nerves or an injection of norepinephrine enhanced the efflux of a PGE-like substance from the rat spleen. Administration of a PG synthetase inhibitor, indomethacin, 100 ng/ml, abolished the efflux of PGE evoked by adrenergic stimuli and potentiated the vasoconstrictor responses to nerve stimulation and to injected norepinephrine. The facilitatory effect of indomethacin on the vasoconstrictor responses to both adrenergic stimuli was abolished by the infusion of PGE2. A PG precursor, arachidonic acid, inhibited the vasoconstrictor responses to nerve stimulation and to injected norepinephrine. Because the inhibitory effect of arachidonic acid was abolished by the administration of indomethacin, it appears to be mediated, at least in part, through the conversion of the acid to a PG(s). These observations and the effect of exogenous PGE compounds suggest that PGs of the E series participate in the modulation of the vascular responses of the rat spleen to adrenergic stimuli. However, the modulatory effect of PGE compounds varies in different vascular beds of rat, viz, facilitatory in renal and mesenteric vasculature and inhibitory in the splenic vasculature. This study also indicates that other products of arachidonic acid metabolism, including PGF2O and TxB2, also may contribute to the modulation of vascular responses to adrenergic stimuli and affect the actions of PGE2 at the adrenergic neuroeffector junction in the rat spleen.