title: Differential effects of olmesartan and ramipril on inflammatory response after myocardial infarction in rats.
abstract: This study compares the effect of two different strategies to inhibit the renin-angiotensin system in the setting of acute myocardial infarction (MI). Male Wistar rats were treated with placebo, the angiotensin-converting enzyme (ACE) inhibitor ramipril (1 mg/kg/day), or the AT1 receptor antagonist, olmesartan (1 mg/kg/day), both initiated 1 week before induction of MI and continued for 6 weeks after MI. The inflammatory reaction in the heart was investigated 7 days post-MI by determination of macrophage infiltration and the expression of tumor necrosis factor (TNF-alpha), interleukin (IL)-1beta and IL-6 at mRNA and protein levels. Six weeks post-MI, cardiac function was measured following chronic implantation of catheters in the LV and femoral artery, and cardiac morphology and coronary structure were investigated in picrosirius-red stained hearts. In placebo-treated rats, macrophage infiltration was accompanied by upregulation of IL-1beta and IL-6 mRNA in the peri-infarct zone. TNF-alpha and IL-1beta mRNA and protein were also upregulated in the non-infarcted myocardium. Whereas both treatment regimes significantly reduced IL-6 upregulation, olmesartan additionally reduced macrophage infiltration and IL-1beta expression. Six weeks post-MI, placebo-treated MI animals developed an impaired cardiac function with structural remodeling of the myocardium and coronaries. While olmesartan and ramipril both improved cardiac function and reduced infarct size and myocardial/coronary remodeling, olmesartan was more effective not only in increasing vascular perimeter, inner vascular diameter and septal thickness but also in lowering media thickness of coronary arteries, inner left ventricular diameter, left ventricular circumference and left ventricular end-diastolic pressure than ramipril. Thus, following MI the AT1 receptor blocker, olmesartan, attenuated cardiac inflammatory reactions and protected myocardial/coronary structure and function of the failing heart proving to be of similar, in some cases superior effectiveness in this respect than the ACE inhibitor, ramipril.
authors.affiliation: Center for Cardiovascular Research (CCR)/Institute of Pharmacology and Toxicology, Charité - University Medicine Berlin, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Sandmann
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Carolin
authors.initials: C
authors.lastname: Fritzenkötter
authors.forename: Johannes
authors.initials: J
authors.lastname: Spormann
authors.forename: Karen
authors.initials: K
authors.lastname: Tiede
authors.forename: Jens W
authors.initials: JW
authors.lastname: Fischer
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002319:Cardiovascular System / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000276:immunology; D010919:Placebos; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D017257:Ramipril / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D007375:Interleukin-1; D015850:Interleukin-6; D010919:Placebos; D012333:RNA, Messenger; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; C437965:olmesartan; D017257:Ramipril