Influence of the new angiotensin converting enzyme inhibitor ramipril on several models of acute inflammation and the adjuvant arthritis in the rat.
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.
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D017257:Ramipril