Interaction of ouabain and diphenylhydantoin (DPH) with the cardiovascular actions of prostaglandin B2 and prostaglandin A2

Several reports have appeared indicating that ouabain may interact at sites on smooth muscle susceptible to activation by prostaglandins. This study reports on the interaction between ouabain (0) and diphenylhydantoin (DPH) with the cardiovascular actions of prostaglandin B₂ (PGB₂) and prostaglandin A₂ (PGA₂). Fifteen μg/kg i.v. of 0 enhanced the pressor response of the canine hindpaw to norepinephrine and tyramine but did not affect the pressor responses to sympathetic nerve stimulation (SNS), PGB₂ or PGA₂. PGB₂-induced bronchoconstriction (mediated solely by stimulation of smooth muscle) was reduced by ouabain. In a separate group of animals not receiving PG before 0, 0 reduced (p<0.05) the pressor responses to PGB₂. DPH enhanced the cutaneous pressor responses to SNS, NE, PGB₂ and PGA₂ but did not affect the bronchoconstrictor response to PGB₂. These data are consistent with the following conclusions: 1) Ouabain antagonizes the smooth muscle contractions produced by PGB₂. 2) The presence of PGB₂ antagonizes the prostaglandin inhibitory effects of ouabain suggesting that PGB₂ may compete for similar sites or allosterically interact with ouabain in smooth muscle. 3) DPH induced enhancement of PGB₂ and PGA₂ induced vasoconstriction may reflect DPH induced enhancement of adrenergic neurotransmitter release or inhibition of transmitter reuptake.