EFFECT OF THE PROSTAGLANDIN SYNTHESIS INHIBITORS INDOMETHACIN AND EICOSA-5,8,1l,14-TETRAYNOIC ACID ON ADRENERGIC RESPONSES IN DOG CUTANEOUS VASCULATURE

¹ Department of Pharmacology, University of Minnesota,Minneapolis,Minnesota

The present study was carried out to determine the effect of the prostaglandin synthesis inhibitors indomethacin and eicosa-5,8,11,14-tetraynoic acid on adrenergic responses in the dog paw perfused at constant blood flow. Low-dose intra-arterial infusions of indomethacin, 3x10-⁶ M, and eicosa-5,8,11,14-tetraynoic acid, 1.5 to 3 x 10^-5 M, into the paw had no significant effect on responses to norepinephrine injected intra-arterially or adrenergic nerve stimulation. Higher dose infusions of indomethacin, 6x10^-6 M, and eicosa-5,8,11,14-tetraynoic acid, 3 to 6x10^-5 M, were effective in potentiating the responses to both norepinephmrine and adrenergic nerve stimulation. There was also a tendency for vasconstriction to occur in the paw after administration of the inhibitors as reflected by a gradual increase in perfusion pressure during the course of these experiments. The adrenergic potentiating effect is not attributable to a blockade of adrenergic uptake by the prostaglandin synthesis inhibitors since in the concentrations employed there was no effect of these agents on the uptake of ³H-norepinephrine by vascular segments in vitro. Infusion of a low dose of prostaglandin E₂ (110 mµg/min) depressed the responses to both norepinephrine and nerve stimulation. These data are consistent with the postulate that an E prostaglandin is synthesized and released in the cutaneous vasculature, and the released prostaglandin antagonizes the vasoconstrictor effect of norepinephrine. When this effect is blocked by the inhibitors, potentiation of the adrenergic responses results.