title: Influence of the new angiotensin converting enzyme inhibitor ramipril on several models of acute inflammation and the adjuvant arthritis in the rat.
abstract: Paw oedema in the rat by carrageenin and kaolin partially caused by Hageman factor activation was potentiated by the new angiotensin converting enzyme (ACE) inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl-L-alanyl]-(lS,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid] (ramipril, Hoe 498) due to its inhibition of kininase II which results in increased bradykinin levels. A dose of 1 microgram ramipril injected into the hind paw of Sprague-Dawley rats concomitantly with, or 1 mg/kg given orally 30 min before administration of the irritants, led to significantly increased inflammatory reactions. The same effects were observed when ramipril was administered 3 h after carrageenin. In the kallikrein-kinin-deficient Brown-Norway rat strain Mai Pfd/f, ramipril did not significantly alter the paw oedema induced as described above. In addition, pretreatment of Sprague-Dawley rats with 10 mg/kg i.v. bromelains completely prevented the potentiation of inflammation by ramipril. Paw oedema provoked by the Hageman factor non-activators serotonin, dextran, ovalbumin and anti-rat IgG was not potentiated by ramipril. The chronic adjuvant arthritis in Lewis rats was not influenced by daily oral treatment with 0.1-3 mg/kg ramipril. Thus, in the rat only those inflammatory reactions involving kinins, presumably generated by Hageman factor activators, are potentiated by ramipril and presumably by other ACE-inhibitors.
mesh_terms: D000208:Acute Disease; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D017257:Ramipril