Angiotensin II receptor type 1 mRNA is upregulated in atria of patients with end-stage heart failure

There is increasing evidence that pathological changes in the myocardium during chronic heart failure (CHF) are partly regulated through the activation of the renin-angiotensin system (RAS), an effect mediated by the angiotensin II type 1 receptor (AT₁R). We examined the expression of cardiac AT₁R mRNA in normal (atria, n = 7; ventricle, n = 3) and end-stage CHF human hearts (atria, n = 8: ventricle, n = 14). Tissue was snap-frozen immediately after explantation during orthotopic cardiac transplantation; control specimens were obtained from healthy donor hearts rejected for technical reasons. Northern blots of purified total mRNA from each tissue were hybridized with a random primed radiolabeled probe for the coding sequence of AT₁R. Stringent conditions were used for both hybridization (5X SSC, 65°C) and washing (0.5X SSC, 0.1% SDS, 65°C) of the membrane. Left and right atrial tissue showed low levels of AT₁R mRNA expression in the controls, with statistically significant upregulation of expression in tissue from pathological hearts; CHF atria 1.28 ± 0.86 optical density (OD) units, control atria 0.56 ± 0.31 OD units. P = 0.05 (mean ± S.D.). There were undetectable levels in ventricles from either control (2/2) or dilated hearts (7/7). The results were independent of the etiology of the heart failure and suggest that increased levels of atrial AT₁R mRNA may occur in response to elevated atrial pressures in heart failure.