The activity of the cardiac renin-angiotensin system is altered in human heart failure, but the regulatory mechanisms are unknown. We analyzed whether angiotensin-converting enzyme (ACE) mRNA expression in heart failure is altered in the atrial myocardium, and whether a correlation exists between atrial ACE mRNA expression and the parameters of left ventricular function. We also investigated whether the use of ACE inhibitors or the ACE I/D genotype modulates the atrial ACE mRNA content. For this purpose patients who were to undergo routine cardiac surgery were selected in a prospective manner according to left ventricular function and ACE inhibitor therapy. Samples of atrial myocardium were taken, and ACE mRNA expression was determined by internally standardized reverse transcription polymerase chain reaction. Atrial ACE mRNA expression did not differ in patients with left ventricular ejection fraction higher than 55% (2423+/-199 copies/ng RNA) and those with a value less than 45% (2661+/-143 copies/ng RNA, n.s.). ACE mRNA expression also did not differ in patients using ACE inhibitors (2585+/-175 copies/ng RNA) and those not using ACE inhibitors (2476+/-185 copies/ng RNA). Furthermore, atrial ACE mRNA expression was not affected by the ACE genotype (DD 2573+/-203, ID 2472+/-215, II 2563+/-249 copies/ng RNA). We conclude that the regulation of atrial ACE mRNA expression occurs predominantly by local mechanical or para- or autocrine factors.