Comparison of the effects of the ace inhibitors trandolapril and enalapril on phlogogen induced foot pad oedema in the rat

Abstract

Two angiotensin converting enzyme (ACE) inhibitors, trandolapril and enalapril, were compared for their effects on rat food-pad oedema induced by carrageenin, bradykinin, dextran and platelet activating factor (PAF). Trandolapril (0.03-30.0 mg/kg, per os) potentiated carrageenin-induced oedemas. Enalapril produced the same effect at 3-10 fold higher doses (0.3-30.0 mg/kg per os). Both ACE inhibitors were equiactive in potentiating bradykinin-induced oedema. Neither compound affected dextran-induced oedema. In marked contrast PAF-induced oedema was reduced by both ACE inhibitors, trandolapril being approximately 10 fold more active than enalapril. The observed differences in potency between the two ACE inhibitors corresponded with their previously described actions on inhibition of plasma and tissue ACE and in inducing hypotension. The results suggest a crucial role of kinins in the oedemagenic response to carrageenin. The reason why the ACE inhibitors reduced PAF-induced oedema is not clear, but could involve peripheral vasodilation.

Could the Pharmacological Differences Observed Between Angiotensin II Antagonists and Inhibitors of Angiotensin Converting Enzyme be Clinically Beneficial?

“…Kinins participate in the process of inflammation and can induce oedema by their effect on vascular permeability, postcapillary venule pressure, and the release of other vasoactive peptides (Wilkin et al 1980;Lindgren et al 1989b;Anderson & deShazo 1990). ACE inhibitors increase the wheal and flare response evoked by transdermal bradykinin, potentiate bradykinin induced foot pad oedema in the rat and increase spontaneous and allergen induced histamine release from skin mast cells in the guinea pig (Lindgren et al 1989a;Jouquey et al 1988). Again, since AT, antagonists do not appear to influence kinin metabolism, they may be devoid of angioedema as a side effect.…”

Profile of the New ACE Inhibitor Trandolapril (RU 44570)

“…induced phlogosis (42), to enhance the depressor response to bradykinin in vivo (10,79), and to potentiate the bradykinin-induced contraction of the guinea pig ileum in vitro (82). However, these data do not necessarily imply a role for kinins in mediating the antihypertensive effects of ACE inhibitors, since the role of kinins in the regulation of blood pressure has still to be determined.…”

“…Since kininase 11, an enzyme converting bradykinin into inactive peptides, is identical to ACE (33), inhibition of kininase II has been proposed to contribute, at least in part, to the pharmacological activity of ACE inhibitors. ACE inhibitors, including trandolapril, have been shown to potentiate bradykinin-induced phlogosis (42), to enhance the depressor response to bradykinin in vivo (10,79), and to potentiate the bradykinin-induced contraction of the guinea pig ileum in vitro (82). However, these data do not necessarily imply a role for kinins in mediating the antihypertensive effects of ACE inhibitors, since the role of kinins in the regulation of blood pressure has still to be determined.…”