Abstract
Renin substrate, biological renin activity, and/or renin-secreting cells in kidneys evolved at an early stage of vertebrate phylogeny. Angiotensin (Ang) I and II molecules have been identified biochemically in representative species of all vertebrate classes, although variation occurs in amino acids at positions 1, 5, and 9 of Ang I. Variations have also evolved in amino acid positions 3 and 4 in some cartilaginous fish. Angiotensin receptors, AT1 and AT2 homologues, have been identified molecularly or characterized pharmacologically in nonmammalian vertebrates. Also, various forms of angiotensins that bypass the traditional renin-angiotensin system (RAS) cascades or those from large peptide substrates, particularly in tissues, are present. Nonetheless, the phylogenetically important functions of RAS are to maintain blood pressure/blood volume homeostasis and ion-fluid balance via the kidney and central mechanisms. Stimulation of cell growth and vascularization, possibly via paracrine action of angiotensins, and the molecular biology of RAS and its receptors have been intensive research foci. This review provides an overview of: (1) the phylogenetic appearance, structure, and biochemistry of the RAS cascade; (2) the properties of angiotensin receptors from comparative viewpoints; and (3) the functions and regulation of the RAS in nonmammalian vertebrates. Discussions focus on the most fundamental functions of the RAS that have been conserved throughout phylogenetic advancement, as well as on their physiological implications and significance. Examining the biological history of RAS will help us analyze the complex RAS systems of mammals. Furthermore, suitable models for answering specific questions are often found in more primitive animals.
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Abbreviations
- ACE:
-
Angiotensin-converting enzyme
- ACTH:
-
Adrenocorticotropic hormone
- Ang:
-
Angiotensin
- AT1 :
-
Ang receptor subtype 1
- AT2 :
-
Ang receptor subtype 2
- BP:
-
Blood pressure
- cAT:
-
Chicken AT1-homologous receptor
- CGP:
-
Ciba-Geigy Peptide (modified peptide angiotensin receptor antagonist)
- E:
-
Embryonic day (specified as E14, E19, etc.)
- FW:
-
Fresh water
- GFR:
-
Glomerular filtration rate
- HR:
-
Heart rate
- i.p.:
-
Intraperitoneal
- ICV:
-
Intracerebroventricular
- IP3 :
-
Inositol triphosphate
- JG:
-
Juxtaglomerular
- L-NAME:
-
Nω-nitro-l-arginine methyl ester
- PG:
-
Prostaglandin
- PRA:
-
Plasma renin activity
- RAS:
-
Renin-angiotensin system
- RT-PCR:
-
Reverse transcriptase-polymerase chain reaction
- SM:
-
Smooth muscle
- SW:
-
Seawater
- tAT:
-
Turkey AT1-homologous receptor
- TGF:
-
Tubuloglomerular feedback
- VSM:
-
Vascular smooth muscle
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Acknowledgments
The author is deeply indebted to Dr. Marty K. S. Wong, Atmosphere and Ocean Research Institute of the University of Tokyo, Kashiwa City, Chiba, Japan, for conceptual suggestions and help. This work was supported by a research grant provided by Niigata University of Health and Welfare, Niigata, Japan, to Hiroko Nishimura.
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Nishimura, H. Renin-angiotensin system in vertebrates: phylogenetic view of structure and function. Anat Sci Int 92, 215–247 (2017). https://doi.org/10.1007/s12565-016-0372-8
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DOI: https://doi.org/10.1007/s12565-016-0372-8