title: Load-induced growth responses in isolated adult rat hearts. Role of the AT1 receptor.
abstract: BACKGROUND
  Stimulation of the angiotensin II type 1 (AT1) receptor by angiotensin II appears to be mandatory for the acute load-induced hypertrophic response of cultured neonatal rat cardiocytes, but its role in the adult heart is controversial. We tested the hypothesis that AT1 receptor blockade will inhibit the acute induction of proto-oncogenes and protein synthesis by the elevation of systolic wall stress in isolated beating adult rat hearts.
  
  
  RESULTS
  Using the established isovolumic perfused heart preparation under constant coronary flow, we found that an increment in left ventricular balloon volume generated an increase in systolic wall stress. The induction of left ventricular c-fos and c-myc mRNA (Northern blotting) was assessed in hearts subjected to increased systolic load without AT1 blockade (No AT1, n = 11) and with AT1 blockade (AT1, n = 11, losartan 40 mg.kg-1.d-1 x 5 days followed by 10(-5) mol/L infusion during perfusion). Flaccid hearts (no left ventricular balloon) served as controls (C, n = 9). The stimulation of new protein synthesis in response to increased systolic load was measured by incorporation of [3H]phenylalanine into cardiac proteins. Elevation of systolic load was associated with a twofold (P < .05) increase in c-fos and c-myc mRNA levels that was not blocked by losartan. The rate of [3H]phenylalanine incorporation into cardiac proteins was increased 2.7-fold (P < .01) in hearts subjected to increased systolic load compared with control hearts. However, AT1 receptor blockade with losartan did not prevent the stimulation of [3H]phenylalanine incorporation (881 +/- 97 versus 923 +/- 82 nmol.g protein-1.h-1, P = NS).
  
  
  CONCLUSIONS
  In contrast with immature myocytes subjected to stretch, the acute growth responses induced by systolic pressure overload in adult rat hearts do not depend on AT1 receptor activation.
authors.affiliation: Charles A. Dana Research Institute, Boston, Mass, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Thienelt
authors.forename: E O
authors.initials: EO
authors.lastname: Weinberg
authors.forename: J
authors.initials: J
authors.lastname: Bartunek
authors.forename: B H
authors.initials: BH
authors.lastname: Lorell
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000254:growth & development* / Q000503:physiopathology*; D006439:Hemodynamics; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D014176:Protein Biosynthesis; D011519:Proto-Oncogenes / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D013314:Stress, Mechanical; D013599:Systole; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D010649:Phenylalanine; D004656:Enalapril; D019808:Losartan