Load-induced growth responses in isolated adult rat hearts. Role of the AT1 receptor

Circulation
C D ThieneltB H Lorell

Abstract

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. 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-fo...Continue Reading

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Citations

Sep 12, 2000·Current Hypertension Reports·L P AudolyT M Coffman
Apr 6, 2000·The American Journal of Cardiology·B H Lorell
Oct 6, 2001·Journal of Cardiovascular Pharmacology·M ShimoyamaC Shigemasa
Mar 11, 2003·The Journal of Physiology·N C SundgrenK L Thornburg
Jul 11, 2001·Biochemical and Biophysical Research Communications·A Yasaka, W Hayashida
Nov 15, 2002·Journal of Molecular and Cellular Cardiology·Pietro Amedeo ModestiGian Gastone Neri Serneri
Sep 1, 2000·Journal of Molecular and Cellular Cardiology·P OliviéroB Ostadal
Oct 19, 2001·Journal of Human Hypertension·H C Routledge, J N Townend
Jun 13, 1998·The Journal of Biological Chemistry·K YamamotoR T Lee
May 12, 1998·The American Journal of Physiology·J J MercadierM Aubier
Apr 8, 1998·The American Journal of Physiology·M HamawakiB A Carabello

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