title: Angiotensin II inhibition increases cellular glucose transport during reperfusion but not ischemia in pig hearts.
abstract: OBJECTIVE
  To study whether ACE inhibition and AT-II receptor blockade modulates myocardial glucose uptake during ischemia and reperfusion.
  
  
  METHODS
  We developed a method for in vivo sampling of large trans-myocardial tissue samples from beating pig hearts and in vitro measurement of sarcolemmal glucose transport, in a series of experiments in which hearts were exposed to stimuli (glucose-insulin and pacing) known to promote cellular glucose transport. In the subsequent study we compared three experimental groups: (i) ACE inhibition (ACE-I, n = 6): increasing oral doses of benazepril up to 40 mg daily for 3 weeks, (ii) angiotensin II receptor antagonist (AT II-A, n = 7): increasing oral doses of valsartan up to 320 mg for 3 weeks, (iii) control (n = 7). Samples were harvested at baseline, following 20 min of regional ischemia, and following 5 and 15 min of reperfusion. The samples were incubated with 3-O-methylglucose (MeGlu), and cellular MeGlu uptake was measured.
  
  
  RESULTS
  Insulin-glucose, pacing, and ischemia increased cellular MeGlu transport two- to fourfold (p < 0.001). Cellular MeGlu transport was increased in ACE-I and AT II-A animals during reperfusion (p < 0.001), but not at baseline or during ischemia, compared with controls.
  
  
  CONCLUSIONS
  Enhanced capacity for glucose transport during reperfusion may be a mechanism underlying the beneficial effects of ACE inhibition and AT II-antagonism in ischemic heart disease.
authors.affiliation: Department of Cardiology, Aarhus Municipal Hospital, University of Aarhus, Denmark. randsbaek@dadlnet.dk
authors.forename: Flemming
authors.initials: F
authors.lastname: Randsbaek
authors.forename: Steen
authors.initials: S
authors.lastname: Lund
authors.forename: Hans Henrik
authors.initials: HH
authors.lastname: Kimose
authors.forename: Erik
authors.initials: E
authors.lastname: Grove
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Ole
authors.initials: O
authors.lastname: Schmitz
authors.forename: Torsten Toftegaard
authors.initials: TT
authors.lastname: Nielsen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D008955:Models, Cardiovascular; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000601:surgery*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012083:Renin / Q000097:blood / Q000187:drug effects; D013552:Swine; D013599:Systole / Q000187:drug effects; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D000804:Angiotensin II; D000255:Adenosine Triphosphate; D006003:Glycogen; D012083:Renin; D005947:Glucose