title: Long-term angiotensin-converting enzyme and angiotensin I--receptor inhibition in pacing-induced heart failure: effects on myocardial interstitial bradykinin levels.
abstract: BACKGROUND
  We examined whether and to what degree long-term angiotensin-converting enzyme (ACE) inhibition, angiotensin type 1 (AT(1))-receptor blockade, or combined inhibition in developing congestive heart failure (CHF) alter myocardial interstitial bradykinin (BF) levels.
  
  
  RESULTS
  Pigs (27-30 kg) underwent rapid pacing-induced CHF (240 bpm, 3 weeks; n = 10); pacing CHF with concomitant ACE inhibition (benezaprilat, 3.75 mg/day; n = 10); pacing CHF and concomitant AT(1)-receptor blockade (valsartan, 60 mg/day; n = 10); pacing CHF and combined inhibition (benezaprilat/valsartan, 1.87/60 mg/day, respectively; n = 10); or served as controls (no pacing, no treatment; n = 10). Steady-state myocardial interstitial BK levels were quantitated by microdialysis. Cardiac output decreased to 1.95 +/- 0.18 L/min in pacing CHF compared with control (3.78 +/- 0.38; P < .05). Cardiac output increased from untreated CHF values with concomitant ACE inhibition (3.91 +/- 0.27 L/min), AT(1)-receptor blockade (3.30 +/- 0.41 L/min), or combined ACE/AT(1)-receptor inhibition (4.13 +/- 0.32 L/min; all P < .05 v CHF). With pacing CHF, myocardial interstitial BK levels were reduced by approximately 50% from control values and were normalized in the ACE inhibition and combined inhibition groups.
  
  
  CONCLUSIONS
  Long-term ACE inhibition increases myocardial interstitial BK levels with CHF; addition of AT(1)-receptor blockade does not seem to abrogate these effects.
authors.affiliation: Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 29427, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Multani
authors.forename: R S
authors.initials: RS
authors.lastname: Krombach
authors.forename: J W
authors.initials: JW
authors.lastname: Hendrick
authors.forename: S C
authors.initials: SC
authors.lastname: Baicu
authors.forename: C
authors.initials: C
authors.lastname: Joffs
authors.forename: J A
authors.initials: JA
authors.lastname: Sample
authors.forename: M
authors.initials: M
authors.lastname: deGasparo
authors.forename: F G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000627:therapeutic use*; D013552:Swine; D013995:Time; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D001920:Bradykinin