(Circulation. 1996;94:1886-1893.)
© 1996 American Heart Association, Inc.
Articles |
Evidence for the Existence of a Functional Cardiac Renin-Angiotensin System in Humans
the Istituto di Clinica Medica Generale e Cardiologia, Center for Heart and Thrombosis Research, University of Florence, Italy.
Correspondence to G.G. Neri Serneri, Istituto di Clinica Medica Generale e Cardiologia, Viale Morgagni 85, 50134 Florence, Italy.
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 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.
Key Words: angiotensin • enzymes • renin
This article has been cited by other articles:
 |
|
 |
|
  R. Jaumdally, C. Varma, R. J. Macfadyen, and G. Y.H. Lip Coronary sinus blood sampling: an insight into local cardiac pathophysiology and treatment? Eur. Heart J., April 2, 2007; 28(8): 929 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Fleming, K. Kohlstedt, and R. Busse New fACEs to the Renin-Angiotensin System Physiology, April 1, 2005; 20(2): 91 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. D. Xiao, S. Fuchs, D. J. Campbell, W. Lewis, S. C. Dudley Jr, V. S. Kasi, B. D. Hoit, G. Keshelava, H. Zhao, M. R. Capecchi, et al. Mice with Cardiac-Restricted Angiotensin-Converting Enzyme (ACE) Have Atrial Enlargement, Cardiac Arrhythmia, and Sudden Death Am. J. Pathol., September 1, 2004; 165(3): 1019 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. C. Luft Cardiac Angiotensin Is Upregulated in the Hearts of Unstable Angina Patients Circ. Res., June 25, 2004; 94(12): 1530 - 1532. [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Carey and H. M. Siragy Newly Recognized Components of the Renin-Angiotensin System: Potential Roles in Cardiovascular and Renal Regulation Endocr. Rev., June 1, 2003; 24(3): 261 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Barlassina, C. Lanzani, P. Manunta, and G. Bianchi Genetics of Essential Hypertension: From Families to Genes J. Am. Soc. Nephrol., November 1, 2002; 13(90003): S155 - 164. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. Ogino, K. Ogura, Y. Kinugasa, Y. Furuse, K. Uchida, M. Shimoyama, T. Kinugawa, S. Osaki, M. Kato, Y. Tomikura, et al. Parathyroid Hormone-Related Protein Is Produced in the Myocardium and Increased in Patients with Congestive Heart Failure J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4722 - 4727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Woods, A. J. Pollard, D. J. Collier, Y. Jamshidi, V. Vassiliou, E. Hawe, S. E. Humphries, and H. E. Montgomery Insertion/Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene and Arterial Oxygen Saturation at High Altitude Am. J. Respir. Crit. Care Med., August 1, 2002; 166(3): 362 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. Neri Serneri, M. Boddi, L. Poggesi, I. Simonetti, M. Coppo, M. L. Papa, G. F. Lisi, M. Maccherini, R. Becherini, A. Boncompagni, et al. Activation of cardiac renin-angiotensin system in unstable angina J. Am. Coll. Cardiol., July 1, 2001; 38(1): 49 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. S. Sibinga and J. A. Ware A Pair of ACEs, for Openers? Circ. Res., September 29, 2000; 87(7): 523 - 525. [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Saris, M. A. van Dijk, I. Kroon, M. A. D. H. Schalekamp, and A. H. J. Danser Functional Importance of Angiotensin-Converting Enzyme-Dependent In Situ Angiotensin II Generation in the Human Forearm Hypertension, March 1, 2000; 35(3): 764 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Kim Measurement of the Renin-Angiotensin System in Heart Failure Biol Res Nurs, January 1, 2000; 1(3): 210 - 226. [Abstract] [PDF]
|
|
|
|
 |
|
 A.H.J. Danser, J. J Saris, M. P Schuijt, and J. P van Kats Is there a local renin--angiotensin system in the heart? Cardiovasc Res, November 1, 1999; 44(2): 252 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Dostal and K. M. Baker The Cardiac Renin-Angiotensin System : Conceptual, or a Regulator of Cardiac Function? Circ. Res., October 1, 1999; 85(7): 643 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. N. Serneri, P. A. Modesti, M. Boddi, I. Cecioni, R. Paniccia, M. Coppo, G. Galanti, I. Simonetti, S. Vanni, L. Papa, et al. Cardiac Growth Factors in Human Hypertrophy : Relations With Myocardial Contractility and Wall Stress Circ. Res., July 9, 1999; 85(1): 57 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. KAGAYA, H. OTANI, T. TANIKAWA, S. NAMIUCHI, S. ISOYAMA, and K. SHIRATO Concentrations of angiotensin II, endothelin-1, and BNP in the coronary sinus and ascending aorta of patients with heart disease Heart, January 1, 1999; 81(1): 102 - 103. [Full Text]
|
|
|
|
 |
|
 S. Hafizi, J. Wharton, K. Morgan, S. P. Allen, A. H. Chester, J. D. Catravas, J. M. Polak, and M. H. Yacoub Expression of Functional Angiotensin-Converting Enzyme and AT1 Receptors in Cultured Human Cardiac Fibroblasts Circulation, December 8, 1998; 98(23): 2553 - 2559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Boddi, L. Poggesi, M. Coppo, N. Zarone, S. Sacchi, C. Tania, and G. G. N. Serneri Human Vascular Renin-Angiotensin System and Its Functional Changes in Relation to Different Sodium Intakes Hypertension, March 1, 1998; 31(3): 836 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. N. Serneri, M. Boddi, I. Cecioni, S. Vanni, M. Coppo, M. L. Papa, B. Bandinelli, I. Bertolozzi, G. Polidori, T. Toscano, et al. Cardiac Angiotensin II Formation in the Clinical Course of Heart Failure and Its Relationship With Left Ventricular Function Circ. Res., May 11, 2001; 88(9): 961 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Neri Serneri, M. Boddi, P. A. Modesti, I. Cecioni, M. Coppo, L. Padeletti, A. Michelucci, A. Colella, and G. Galanti Increased Cardiac Sympathetic Activity and Insulin-Like Growth Factor-I Formation Are Associated With Physiological Hypertrophy in Athletes Circ. Res., November 23, 2001; 89(11): 977 - 982. [Abstract] [Full Text] [PDF]
|
|