Enalaprilat, but not cilazaprilat, increases inflammatory skin reactions in guinea-pigs.
The inflammatory effects of enalaprilat and cilazaprilat were tested in an experimental model of ovalbumin-sensitised guinea-pigs. Enalaprilat, but not cilazaprilat, enhanced the ovalbumin-induced inflammatory skin responses. The effect of enalaprilat was dose-dependent. Enalaprilat significantly increased the skin content of substance P and histamine. Cilazaprilat did not alter the level of these inflammatory mediators. Enalaprilat, applied locally, but not cilazaprilat, enhanced the inflammatory reactions caused by intradermal injections of allergen and substance P. Both angiotensin converting enzyme (ACE) inhibitors enhanced the inflammatory skin response evoked by bradykinin. Our study strongly indicates that enalaprilat has pro-inflammatory properties, whereas the new long-acting ACE inhibitor cilazaprilat does not. This might give a better safety profile of cilazaprilat.
Andersson
R G
RG
Department of Pharmacology, Faculty of Health Sciences, Linköping University, Sweden.
Karlberg
B E
BE
Lindgren
B R
BR
Persson
K
K
Rosenqvist
U
U
D000485:Allergens / Q000276:immunology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D017315:Cilazapril / Q000031:analogs & derivatives*; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D015773:Enalaprilat / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011724:Pyridazines / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism
D000485:Allergens; D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; D013373:Substance P; D006632:Histamine; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; C045980:cilazaprilat