Summary
To understand the significance of the tissue renin-angiotensin system in the heart, we examined the expression of renin and angiotensin-converting enzyme (ACE) in autopsied human hearts. Samples were taken from organs obtained at autopsy from 15 patients without heart disease and 3 patients with heart disease (old myocardial infarctions, acute myocardial infarctions, and hypertrophic cardiomyopathy). We examined the expression of renin and ACE mRNA by using the reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR showed the expression of renin in the right atria in all patients. However, expression of renin mRNA in the left ventricles was not found in any of the 15 hearts without heart disease. In contrast, renin mRNA was detected in the left ventricles in hearts with heart disease. ACE mRNA was detected in both the atria and the ventricles in normal hearts, and its expression did not alter in diseased hearts. These findings suggest that renin mRNA is expressed mainly in the right atria in normal hearts, but that is expression in the left ventricle can be activated in some pathological conditions.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Dzau VJ, Ellison KE, Brody T, Ingelfinger J, Pratt RE (1987) A comparative study of the distributions of renin and angiotensinogen messenger ribonucleic acids in rat and mouse tissues. Endocrinology 120:2334–2338
Unger T, Gohlke P (1990) Tissue renin-angiotensin systems in the heart and vasculature: Possible involvement in the cardiovascular actions of converting enzyme inhibitors. Am J Cardiol 65:3I-10I
Schunkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS, Lorell BH (1990) Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. J Clin Invest 86:1913–1920
Sawa H, Tokuchi F, Mochizuki N, Endo Y, Furuta Y, Shinohara T, Takada A, Kawaguchi H, Yasuda H, Nagashima K (1992) Expression of the angiotensinogen gene and localization of its protein in the human heart. Circulation 86:138–146
Lindpaintner K, Ganten D (1991) The cardiac renin-angiotensin system: An appraisal of present experimental and clinical evidence. Circ Res 68:905–921
Studer R, Reinecke H, Müller B, Holtz J, Just H, Drexler H (1994) Increased angiotensin-I converting enzyme gene expression in the failing human heart. Quantification by competitive RNA polymerase chain reaction. J Clin Invest 94:301–310
Boer PH, Ruzicka M, Lear W, Harmsen E, Rosenthal J, Leenen FHH (1994) Stretch-mediated activation of cardiac renin gene. Heart Circ Physiol 36:H1630-H1636
Dzau VJ, Re R (1994) Tissue angiotensin system in cardiovascular medicine, a paradigm shift? Circulation 89:493–498
Baker KM, Booz GW, Dostal DE (1992) Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system. Annu Rev Physiol 54:227–241
Paul M, Backmann J, Ganten D (1992) The tissue renin-angiotensin systems in cardiovascular disease. Trends Cardiovasc Med 2:94–99
Dostal DE, Baker KM (1993) Evidence for a role of an intracardiac renin-angiotensin system in normal and failing hearts. Trends Cardiovasc Med 3:67–74
Sawa H, Kawaguchi H, Mochizuki N, Endo Y, Tokuchi F, Fujioka Y, Nagashima K, Kitabatake A (1994) Distribution of angiotensinogen in diseased human hearts. Mol Cell Biochem 132:15–23
Paul M, Wagner J, Dzau VJ (1993) Gene expression of the renin-angiotensin system in human tissues. Quantitative analysis by the polymerase chain reaction. J Clin Invest 91:2058–2064
Morgan K, Wharton J, Webb JC, Keogh BE, Smith PL, Taylor KM, Oakley CM, Polak JM, Cleland JG (1994) Co-expression of renin-angiotensin system component genes in human atrial tissue. J Hypertens [Suppl] 12:S11-S19
von Lutterotti N, Catanzaro DF, Sealey JE, Laragh JH (1994) Renin is not synthesized by cardiac and extrarenal vascular tissues. A review of experimental evidence. Circulation 89:458–470
Danser AHJ, van Kats JP, Admiraal PJJ, Derkx FHM, Lamers JMJ, Verdouw PDV, Saxena PR, Schalekamp MADH (1994) Cardiac renin and angiotensins. Uptake from plasma versus in situ synthesis. Hypertension 24:37–48
Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenolchloroform extraction. Anal Biochem 162:156–159
Imai T, Miyazaki H, Hirose S, Hori H, Hayashi T, Kageyama R, Ohkubo H, Nakanishi S, Murakami K (1983) Cloning and sequence analysis of cDNA for human renin precursor. Proc Natl Acad Sci USA 80: 7405–7409
Veres G, Gibbs RA, Scherer SE, Caskey CT (1987) The molecular basis of the sparse fur mouse mutation. Science 237:415–417
Mullis KB, Faloona FA, Scharf SJ, Saiki RK, Horn GT, Erlich HA (1986) Specific enzymatic amplification of DNA in vitro: The polymerase chain reaction. Cold Spring Harbor Symp Quant Biol 51:335–350
Hubert C, Houot AM, Corvol P, Soubrier F (1991) Structure of the angiotensin I-converting enzyme gene: Two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem 266:15377–15383
Lanzillo JJ (1991) Chemiluminescent nucleic acid detection with digoxigenin-labeled probes: A model system with probes for angiotensin converting enzyme which detect less than one attomole of target DNA. Anal Biochem 194:45–53
Fukamizu A, Uehara S, Sugimura K, Kon Y, Sugimura M, Hasegawa T, Yokoyama M, Nomura T, Katsuki M, Murakami K (1991) Cell type-specific expression of the human renin gene. J Biol Regul Homeost Agents 5:112–116
Defendini R, Zimmerman EA, Weare JA, Alhenc-Gelas F, Erdös EG (1983) Angiotensin-converting enzyme in epithelial and neuroepithelial cells. Neuroendocrinology 37:32–40
Lou Y, Robinson BG, Morris BJ (1993) Renin messenger RNA, detected by polymerase chain reaction, can be switched on in rat atrium. J Hypertens 11:237–243
Caldwell P, Seegal B, Hsu K, Das M, Soffer R (1976) Angiotensin-converting enzyme: Vascular endothelial localization. Science 191:1050–1051
The SOLVD investigators (1992) Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327:685–691
Pfeffer MA, Lamas GA, Vaughan DE, Parisi AF, Braunwald E (1988) Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med 319:80–86
Hirsch AT, Talsness CE, Schunkert H, Paul M, Dzau VJ (1991) Tissue-specific activation of cardiac angiotensin-converting enzyme in experimental heart failure. Circ Res 69:475–482
Schunkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS, Lorell BH (1990) Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. J Clin Invest 86:1913–1920
Urata H, Healy B, Stewart RW, Bumpus FM, Husain A (1989) Angiotensin II receptors in normal and failing human hearts. J Clin Endocrinol Metab 69:54–66
Mochizuki N, Sawa H, Yasuda H, Shinohara T, Nagashima K, Yamaji T, Ohnuma N, Hall WW (1991) Distribution of atrial natriuretic peptide in the conduction system and ventricles of the human heart. Virchows Arch [A] 418:9–16
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Endo-Mochizuki, Y., Mochizuki, N., Sawa, H. et al. Expression of renin and angiotensin-converting enzyme in human hearts. Heart Vessels 10, 285–293 (1995). https://doi.org/10.1007/BF02911386
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02911386