title: Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade prevent cardiac remodeling in pigs after myocardial infarction: role of tissue angiotensin II.
abstract: BACKGROUND
  The mechanisms behind the beneficial effects of renin-angiotensin system blockade after myocardial infarction (MI) are not fully elucidated but may include interference with tissue angiotensin II (Ang II).
  
  
  RESULTS
  Forty-nine pigs underwent coronary artery ligation or sham operation and were studied up to 6 weeks. To determine coronary angiotensin I (Ang I) to Ang II conversion and to distinguish plasma-derived Ang II from locally synthesized Ang II, (125)I-labeled and endogenous Ang I and II were measured in plasma and in infarcted and noninfarcted left ventricle (LV) during (125)I-Ang I infusion. Ang II type 1 (AT(1)) receptor-mediated uptake of circulating (125)I-Ang II was increased at 1 and 3 weeks in noninfarcted LV, and this uptake was the main cause of the transient elevation in Ang II levels in the noninfarcted LV at 1 week. Ang II levels and AT(1) receptor-mediated uptake of circulating Ang II were reduced in the infarct area at all time points. Coronary Ang I to Ang II conversion was unaffected by MI. Captopril and the AT(1) receptor antagonist eprosartan attenuated postinfarct remodeling, although both drugs increased cardiac Ang II production. Captopril blocked coronary conversion by >80% and normalized Ang II uptake in the noninfarcted LV. Eprosartan did not affect coronary conversion and blocked cardiac Ang II uptake by >90%.
  
  
  CONCLUSIONS
  Both circulating and locally generated Ang II contribute to remodeling after MI. The rise in tissue Ang II production during angiotensin-converting enzyme inhibition and AT(1) receptor blockade suggests that the antihypertrophic effects of these drugs result not only from diminished AT(1) receptor stimulation but also from increased stimulation of growth-inhibitory Ang II type 2 receptors.
authors.affiliation: Department of Internal Medicine I, Erasmus University Rotterdam, Rotterdam, the Netherlands.
authors.forename: J P
authors.initials: JP
authors.lastname: van Kats
authors.forename: D J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: D B
authors.initials: DB
authors.lastname: Haitsma
authors.forename: M P
authors.initials: MP
authors.lastname: Schuijt
authors.forename: R
authors.initials: R
authors.lastname: Niebuur
authors.forename: R
authors.initials: R
authors.lastname: Stubenitsky
authors.forename: F
authors.initials: F
authors.lastname: Boomsma
authors.forename: M A
authors.initials: MA
authors.lastname: Schalekamp
authors.forename: P D
authors.initials: PD
authors.lastname: Verdouw
authors.forename: A H
authors.initials: AH
authors.lastname: Danser
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D002216:Captopril / Q000097:blood; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000097:blood*; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000097:blood*; D013552:Swine
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D002216:Captopril; D007703:Peptidyl-Dipeptidase A