DISSIMILARITY BETWEEN PROSTAGLANDIN E(1) AND NITRIC-OXIDE DONORS AS POTENTIATORS OF PLASMA EXUDATION IN THE RABBIT SKIN IN-VIVO

The ability of prostaglandin E(1) (PGE(1)) and nitric oxide (NO) donor compounds such as sodium nitroprusside (SNP), glyceryl trinitrate (GT N), and 3-morpholino-sydnonimine (SIN-1) to modulate the histamine- an d bradykinin-induced increase in microvascular permeability have been investigated in rabbit skin, The effect of the NO synthesis inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on the plasma exudation induced by histamine and bradykinin was also studied. Local edema for mation was evaluated using [I-125]human serum albumin, New Zealand whi te rabbits received an intravenous injection of [I-125]human albumin f ollowed immediately by the intradermal injection of edematogenic agent s into the shaved dorsolateral skin. PGE(1) (0.1 nmol/site) significan tly potentiated both histamine- and bradykinin-induced edema. In contr ast, 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 eith er histamine or bradykinin. GTN (0.4-40 nmol/site) also had no effect on the increase in plasma exudation induced by histamine and bradykini n in the presence of PGE(1). L-NAME (50-400 nmol/site), but not its en antiomer D-NAME, dose-dependently reduced the edema formation induced by a combination of either histamine or bradykinin with PGE(1). This i nhibition was significantly reversed by SNP (4-400 nmol/site) and by h igh doses (2.5 mu mol/site) of L-arginine (but not by D-arginine). Our results thus demonstrate that PGE(1), 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 L-NAME-induced inhibition of the edema provoked by histamine. Rather, this difference most likely reflects the ability of PGE(1) to modulat e vascular permeability by mechanism(s) other than an increase in arte rial flow.