Evidence for the Existence of a Functional Cardiac Renin-Angiotensin System in Humans

Author:

Serneri Gian Gastone Neri1,Boddi Maria1,Coppo Mirella1,Chechi Tania1,Zarone Nicoletta1,Moira Martelli1,Poggesi Loredana1,Margheri Massimo1,Simonetti Ignazio1

Affiliation:

1. the Istituto di Clinica Medica Generale e Cardiologia, Center for Heart and Thrombosis Research, University of Florence, Italy.

Abstract

Background 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. Methods and Results 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 125 I-angiotensin I and 125 I-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, 125 I-angiotensin II extraction did not change, the cardiac fractional conversion rate of 125 I-angiotensin I to 125 I-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. Conclusions These results provide evidence for the existence of a functional cardiac RAS independent of but related to the circulating RAS.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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