The Fate of Angiotensin II in Placental Tissue and Blood

Abstract

The existence of a non-canonical pathway of renin-angiotensin system in the blood pressure control system has been highlighted over the past three decades. The enzymes involved in this pathway include a series of angiotensinases such as neprilysin (NEP), aminopeptidase A (APA), carboxypeptidase, and angiotensin converting enzyme 2. The physiological roles of these peptidases have been reconsidered in this study, based on the publications of other research groups and the results from our previous study, regarding the liberation of constituent amino acids from angiotensin II by placenta tissue and blood serum, respectively.

Key words

pregnancy - hypertension - renin-angiotensin system - neprilysin - aminopeptidase A - angiotensin convertingenzyme

Publication History

Received: 19 September 2023

Accepted after revision: 01 November 2023

Accepted Manuscript online:
01 November 2023

Article published online:
11 December 2023

• References

• 1 Mizutani S, Akiyama H, Kurauchi O. et al. In vitro degradation of angiotensin II (A-II) by human placental subcellular fractions, pregnancy sera and purified placental aminopeptidases. Acta Endocrinol 1985; 110: 135-139
• 2 Mizutani S, Okano K, Hasegawa E. et al. Aminopeptidase A in human placenta. Biochim Biophys Acta 1981; 678: 168-178
• 3 Chevallier S, Goeltz P, Thibault P. et al. Characterization of a prolyl endopeptidase from Flavobacterium meningosepticum. Complete sequence and localization of the active-site serine. J Biol Chem 1992; 267: 8192-8199
• 4 Mizutani S, Sumi S, Suzuki O. et al. Post-proline endopeptidase in human placenta. Biochim Biophys Acta 1984; 786: 113-117
• 5 Stephenson SL, Kenny AJ. Metabolism of neuropetides hydrolysis of the angiotensins, bradykinin, substance P and oxytocin by pig kidney microvillar membranes. Biochem J 1987; 241: 237-247
• 6 Webster CI, Burrell M, Olsson L-L. et al. Engineering neprilysin activity to create a novel therapeutic for Alzheimer’s disease. PLoS One 2014; 9: e104001
• 7 Vickers C, Hales P, Kaushik V. et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem 2002; 277: 14838-14843
• 8 Rice GI, Thomas DA, Grant PJ. et al. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochm J 2004; 383: 45-51
• 9 Sakura H, Lin TY, Doi M. et al. Purification and properties of oxytocinase, a metalloenzyme. Biochem Intern 1981; 2: 173-179
• 10 Kurauchi O, Mizutani S, Okano K. et al. Purification and characterization of human placental microsomal aminopeptidase: immunological difference between placental microsomal aminopeptidase and pregnancy serum cystyl-aminopeptidase. Enzyme 1986; 35: 197-205
• 11 Li Q, Zhang L, Pfaffendorf M. et al. Comparative effects of angiotensin II and its degradation products angiotensin III and angiotensin IV in rat aorta. Br J Pharmacol 1995; 116: 2963-2970
• 12 Mizutani S, Yamada R, Kurauchi O. et al. Serum aminopeptidase A (AAP) in normal pregnancy and pregnancy complicated by pre-eclampsia. Arch Gynecol 1987; 240: 27-31
• 13 Rogi T, Tsujimoto M, Nakazato H. et al. Human placental leucine aminopeptidase/oxytocinase. A new member of type II membrane-spanning zinc metallopeptidase family. J Biol Chem 1996; 271: 56-61
• 14 Yamahara N, Nomura S, Suzuki T. et al. Placental leucine aminopeptidase/oxytocinase in maternal serum and placenta during normal pregnancy. Life Sci 2000; 66: 1401-1410
• 15 Kozaki H, Itakura A, Okamura M. et al. Maternal serum placental leucine aminopeptidase (P-LAP)/oxytocinase and preterm delivery. Int J Gynecol Obstet 2001; 73: 207-213
• 16 Swales JD, Tange JD, Thurston H. Vascular angiotensin II receptors and sodium balance in rats. Circ Res 1975; 37: 96-100
• 17 Pipkin FB. The renin-angiotensin system in pre-eclampsia. In: Lyall F, Belfort M (eds). Pre-eclampsia etiology and clinical practice. Cambridge: Cambridge University Press; 2007: 78-91
• 18 Pueyo ME, Michel J-B. Angiotensin II receptors in endothelial cells. Gen Pharmac 1997; 29: 691-696
• 19 Harata T, Ando H, Iwase A. et al. Localization of angiotensin II, the AT1 receptor, angiotensin-converting enzyme, aminopeptidase A, adipocyte-derived leucine aminopeptidase, and vascular endothelial growth factor in the human ovary throughout the menstrual cycle. Fertil Steril 2006; 86: 433-439
• 20 Aumelas A, Sakarellos C, Lintner K. et al. Studies on angiotensin II and analogs: Impact of substitution in position 8 on conformation and activity. Proc Natl Acad Sci U S A 1985; 82: 1881-1885
• 21 Firiou F, Lintner K, Fermandjian S. et al. Amino acid side chain conformation in angiotensin II and analogs: correlated results of circular dichroism and ¹H nuclear magnetic resonance. Proc Natl Acad Sci U S A 1980; 77: 82-86
• 22 Asada H, Horita S, Hirata K. et al. Crystal structure of the human angiotensin II type 2 receptor bound to an angiotensin II analog. Nat Struct Mol Biol 2018; 25: 570-576
• 23 Rice GI, Jones AL, Grant PJ. et al. Circulating activities of angiotensin-converting Enzyme, its homologue, angiotensin-converting enzyme 2, and neprilysin in a family study. Hypertension 2006; 48: 914-920
• 24 Tamanna S, Clifton VL, Rae K. et al. Angiotensin converting enzyme 2(ACE2) in pregnancy and small for gestational age. Front Physiol 2020; 11: 590787
• 25 Bharadwaj MS, Strawn WB, Groban L. et al. Angiotensin-converting enzyme 2 deficiency is associated with impaired gestational weight gain and fetal growth restriction. Hypertension 2011; 58: 852-828
• 26 Campbell DJ, Zeitz CJ, Esler MD. et al. Evidence against a major role for angiotensin converting enzyme-related carboxypeptidase (ACE2) in angiotensin peptide metabolism in the human coronary circulation. J Hypertens 1971; 22: 1971-1976
• 27 Reudelhuber TL. A place in our hearts for the lowly angiotensin1-7 peptide?. Hypertension 2006; 47: 811-815
• 28 Wysocki J, Ye M, Battle D. Plasma and kidney angiotensin peptides: importance of the aminopeptidase A/angiotensin III axis. Am J Hypertens 2015; 28: 1418-1426
• 29 Ocaranza MP, Riquelme JA, Garcia L. et al. Counter-regulatory renin-angiotensin system in cardiovascular disease. Nat Rev Cardiol 2020; 17: 116-129