Article ; Online: Circulating renin-angiotensin systems mediated feedback controls over the mean-arterial pressure.
Journal of theoretical biology
2023 Volume 572, Page(s) 111589
Abstract: The renin-angiotensin systems play pivotal role in cardiovascular physiology through its effects on regulating blood pressure and electrolyte homeostasis. Components of circulating RAS (cRAS) that include precursor angiotensinogen, two critical enzymes ( ... ...
| Abstract | The renin-angiotensin systems play pivotal role in cardiovascular physiology through its effects on regulating blood pressure and electrolyte homeostasis. Components of circulating RAS (cRAS) that include precursor angiotensinogen, two critical enzymes (renin and angiotensin-converting enzyme, ACE), their bioactive products, angiotensin- I, II together with its receptors (AT1R and AT2R) essentially determine this homeostasis. Most classical studies, however, showed the deleterious role of cRAS in elevating the blood pressure. Contemporary discovery of non-canonical components of the RAS has challenged this classic hypothesis that it can only exert deleterious effects on the cardiovascular systems. Using the classic cRAS model, we have designed in-silico experiments to test the hypothesis that AT2R-mediated feedback effects play pivotal role for maintaining the normal variation of the mean-arterial pressure (MAP).Beside the AT2R-mediation of downstream singling pathways consisting of several non-canonical RAS components, this study first time illustrated AT2R mediated feedback controls over the blood pressure regulation: one that impedes AT1R activity, and the other that downregulates renin. It has been shown that relatively stronger suppression of renin activity significantly contributes in maintaining the normal MAP and that tight AT2R-mediated regulation is relaxed in hyper-and hypotension. This control mechanism is noted to be robustly maintained with the MAP variations through an established linear steady-state relationship among renin, angiotensin I and angiotensin II. This examination suggests that AT2R-mediated downregulation of renin activities potentially counteracts the AT1R-mediated deleterious actions of Ang II. This study, therefore, provides a solid ground for considering different AT2 receptor adaptor protein and direct agonism at AT2R that can cause greater effects along with contemporary approaches of blocking AT1R mediation to attenuate hypertension or other cardiovascular disorders. |
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| MeSH term(s) | Renin/metabolism ; Feedback ; Arterial Pressure ; Renin-Angiotensin System/physiology ; Angiotensin II/metabolism | |||||
| Chemical Substances | Renin (EC 3.4.23.15) ; Angiotensin II (11128-99-7) | |||||
| Language | English | |||||
| Publishing date | 2023-07-31 | |||||
| Publishing country | England | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 2972-5 | |||||
| ISSN | 1095-8541 ; 0022-5193 | |||||
| ISSN (online) | 1095-8541 | |||||
| ISSN | 0022-5193 | |||||
| DOI | 10.1016/j.jtbi.2023.111589 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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