title: The angiotensin II AT1 receptor antagonist candesartan at antihypertensive plasma concentrations reduces damage induced by ischemia-reperfusion.
abstract: The aim of this study was to investigate if the angiotensin II AT1 receptor antagonist candesartan in antihypertensive plasma concentrations improves myocardial function and limits infarct size in anesthetized pigs. Animals were subjected to 45 min of regional ischemia and 240 min of reperfusion. Starting 60 min before ischemia, two groups of pigs (n = 6 in each) received either candesartan (25 micrograms/kg bolus followed by a continuous infusion at a rate of 14 micrograms/kg/h) or the corresponding volume of vehicle throughout the study period. Left ventricular systolic segment shortening (%SS) was measured by sonomicrometry, and infarct size was determined by triphenyl tetrazolium chloride staining. The plasma concentration of candesartan during the experiment was between 100 and 150 nmol/L, which was considered to be within the therapeutic range. Neither candesartan nor vehicle affected hemodynamics or coronary blood flow prior to ischemia. Compared to vehicle, candesartan improved recovery of %SS in the ischemic area. At 240 min of reperfusion, the %SS was significantly higher in pigs given candesartan than in pigs given vehicle (7.1 +/- 0.87% vs-1 +/- 1.79%; p < 0.01). In both groups the area at risk was approximately 20% of the left ventricle. Infarct size as a percentage of the area at risk was significantly smaller in the candesartan group than in the vehicle group (46 +/- 3.0 vs 73 +/- 3.6%; p < 0.01). The results suggest that angiotensin II AT1 receptor blockade, obtained in antihypertensive plasma concentrations, supports myocardial functional recovery and limits infarct size.
authors.affiliation: Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
authors.forename: Q D
authors.initials: QD
authors.lastname: Wang
authors.forename: P O
authors.initials: PO
authors.lastname: Sjöquist
authors.forename: L
authors.initials: L
authors.lastname: Rydén
mesh_terms: D000758:Anesthesia; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D003331:Coronary Vessels / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D009203:Myocardial Infarction / Q000517:prevention & control*; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; C081643:candesartan