Activation of cardiac renin-angiotensin system in unstable angina

OBJECTIVES The aim of this study was to investigate the activity of the car diac renin-angiotensin system (RAS) in unstable angina (UA). BACKGROUND Angiotensin (Ang) II locally produced by continuously operating cardiac RAS may affect the pathophysiology of UA. METHODS In 35 patients with UA, 32 with stable effort angina (SA) and 21 wi th atypical chest pain (controls), cardiac RAS was investigated during coro nary angiography after five days of Holter monitoring by combining the meas urement of aorta-coronary sinus gradient for Ang I and Ang II with the kine tics study of I-125-Ang I. Messenger RNAs (mRNA) for all the components of RAS were also quantified with the reverse transcriptase-polymerase chain re action (RT-PCR) and localized by in situ hybridization in myocardial biopsy specimens from patients who underwent aorta-coronary bypass surgery. RESULTS Cardiac Ang II generation was higher in patients with UA than it wa s in patients with SA or in controls (p < 0.001) due to increased de novo c ardiac Ang I formation and its enhanced fractional conversion rate to Ang I I. Messenger RNA levels for angiotensinogen (AGTN), angiotensin-converting enzyme (ACE) and Ang II type 1 (AT1) subtype receptors were higher in patie nts with UA (p < 0.01) than they were in patients with SA or in control hea rts. Messenger RNAs for AGTN and ACE were almost exclusively expressed on e ndothelial and interstitial cells. Angiotensin II formation was correlated with ischemia burden (p < 0.001). However, the amount of Ang II formed and the expression levels of mRNAs for AGTN, ACE and AT1 were not related to th e time that had elapsed since the last anginal attack. CONCLUSIONS In patients with UA, cardiac RAS is activated, resulting in inc reased Ang II formation. Myocardial ischemia is essential for RAS activatio n, but it is unlikely to be a direct and immediate cause of RAS activation. (J Am Coil Cardiol 2001;38:49-55) (C) 2001 by the American College of Card iology.