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


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 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.


CONCLUSIONS
These results provide evidence for the existence of a functional cardiac RAS independent of but related to the circulating RAS.
Neri Serneri
G G
GG
Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Italy.
Boddi
M
M
Coppo
M
M
Chechi
T
T
Zarone
N
N
Moira
M
M
Poggesi
L
L
Margheri
M
M
Simonetti
I
I
D000328:Adult; D000803:Angiotensin I / Q000097:blood / Q000493:pharmacokinetics; D000804:Angiotensin II / Q000097:blood / Q000493:pharmacokinetics; D000809:Angiotensins / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D003326:Coronary Circulation; D004039:Diet, Sodium-Restricted; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis; D012084:Renin-Angiotensin System / Q000502:physiology*; D014018:Tissue Distribution
D000809:Angiotensins; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I