Evidence for the existence of a functional cardiac renin-angiotensin system in humans

• Published in: Circulation (New York, N.Y.) Vol. 94; no. 8; pp. 1886 - 1893
• Main Authors: NERI SERNERI, G. G, BODDI, M, COPPO, M, CHECHI, T, ZARONE, N, MOIRA, M, POGGESI, L, MARGHERI, M, SIMONETTI, I
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 15.10.1996; American Heart Association, Inc
• Subjects: Adult; Angiotensin I - blood; Angiotensin I - pharmacokinetics; Angiotensin II - blood; Angiotensin II - pharmacokinetics; Angiotensins - analysis; Biological and medical sciences; Chromatography, High Pressure Liquid; Coronary Circulation; Diet, Sodium-Restricted; Female; Fundamental and applied biological sciences. Psychology; Heart; Humans; Male; Middle Aged; Myocardium - chemistry; Myocardium - metabolism; Peptide Fragments - analysis; Renin-Angiotensin System - physiology; Tissue Distribution; Vertebrates: cardiovascular system; Heart; Human; Renin angiotensin system; Sodium; Exploration; Circulatory system; Hemodynamics
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.94.8.1886

The presence of mRNA for the essential components of the renin-angiotensin system (RAS) has been found in animal and human hearts. The present study was designed to provide evidence for the existence of a (functional) cardiac RAS. Twenty-four patients with atypical chest pain undergoing coronary angiography for diagnostic purposes were investigated. The cardiac production rate of angiotensins was estimated by measurement of the cardiac extraction of 125I-angiotensin I and 125I-angiotensin II associated with the determination of endogenous angiotensins in aortic and coronary sinus blood in normal, low, or high sodium diets. In a normal sodium diet, angiotensin I and II aorta-coronary sinus gradients were tendentially negative (-1.8 +/- 2.5 and -0.9 +/- 1.7 pg/mL, respectively), and the amounts of angiotensin I and II added by cardiac tissues were 6.5 +/- 3.1 and 2.7 +/- 1.3 pg/mL, respectively. The low sodium diet caused a significant increase in both plasma renin activity (PRA) and angiotensin I concentration in aortic but not in coronary sinus blood, resulting in a more negative aorta-coronary sinus gradient (-9.7 +/- 3.1 pg/mL, P < .01). Angiotensin formation by PRA in blood during transcardiac passage increased (P < .001), whereas angiotensin I formed by cardiac tissues decreased dramatically. Accordingly, in the low sodium diet, 125I-angiotensin II extraction did not change, the cardiac fractional conversion rate of 125I-angiotensin I to 125I-angiotensin II notably decreased (P < .01), and angiotensin II formation by cardiac tissues was undetectable. The high sodium diet caused a decrease in PRA and no changes in cardiac extraction of radiolabeled angiotensins; conversely, angiotensin I formed by cardiac tissues, cardiac Ang I fractional conversion rate, and angiotensin II formed during transcardiac passage significantly (P < .01 for all) increased. These results provide evidence for the existence of a functional cardiac RAS independent of but related to the circulating RAS.