Dissimilarity between prostaglandin E1 and nitric oxide donors as potentiators of plasma exudation in the rabbit skin in vivo

The ability of prostaglandin E₁ (PGE₁) and nitric oxide (NO) donor compounds such as sodium nitroprusside (SNP), glyceryl trinitrate (GTN), and 3-morpholino-sydnonimine (SIN-1) to modulate the histamine- and bradykinin-induced increase in microvascular permeability have been investigated in rabbit skin. The effect of the NO synthesis inhibitor N^ω-nitro- -arginine methyl ester ( -NAME) on the plasma exudation induced by histamine and bradykinin was also studied. Local edema formation was evaluated using ¹²⁵I]human serum albumin. New Zealand white rabbits received an intravenous injection of ¹²⁵I]human albumin followed immediately by the intradermal injection of edematogenic agents into the shaved dorsolateral skin. PGE₁ (0.1 nmol/site) significantly potentiated both histamine- and bradykinin-induced edema. In contrast, SNP (0.4–400 nmol/site), SIN-1 (0.4–400 nmol/site), and GTN (0.4–40 nmol/site) did not affect the edematogenic response induced by either histamine or bradykinin. GTN (0.4–40 nmol/site) also had no effect on the increase in plasma exudation induced by histamine and bradykinin in the presence of PGE₁. -NAME (50–400 nmol/site), but not its enantiomer -NAME, dose-dependently reduced the edema formation induced by a combination of either histamine or bradykinin with PGE₁. This inhibition was significantly reversed by SNP (4–400 nmol/site) and by high doses (2.5 μmol/site) of -arginine (but not by -arginine). Our results thus demonstrate that PGE₁, but not nitrovasodilators, can actually potentiate histamine- and bradykinin-induced edema in rabbit skin. This discrepancy cannot be explained by the lack of vasodilator activity of the nitrovasodilators since these were able to reverse the -NAME-induced inhibition of the edema provoked by histamine. Rather, this difference most likely reflects the ability of PGE₁ to modulate vascular permeability by mechanism(s) other than an increase in arterial flow.