Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

Angiotensin II, dopamine and nitric oxide. An asymmetrical neurovisceral interaction between brain and plasma to regulate blood pressure

1 Department of Health Sciences, University of Jaén, Jaén, Spain
2 Cardiovascular and Metabolic Syndrome Adviser, Rossemaison, Switzerland

Special Issues: Special Issue on Neuronal Nitric Oxide

Vital functions, such as blood pressure, are regulated within a framework of neurovisceral integration in which various factors are involved under normal conditions maintaining a delicate balance. Imbalance of any of these factors can lead to various pathologies. Blood pressure control is the result of the balanced action of central and peripheral factors that increase or decrease. Special attention for blood pressure control was put on the neurovisceral interaction between Angiotensin II and the enzymes that regulate its activity as well as on nitric oxide and dopamine. Several studies have shown that such interaction is asymmetrically organized. These studies suggest that the neuronal activity related to the production of nitric oxide in plasma is also lateralized and, consequently, changes in plasma nitric oxide influence neuronal function. This observation provides a new aspect revealing the complexity of the blood pressure regulation and, undoubtedly, makes such study more motivating as it may affect the approach for treatment.
  Article Metrics


1.Oparil S, Acelajado MC, Bakris GL, et al. (2018) Hypertension. Nat Rev Dis Primers 4: 18014.    

2.Prieto I, Villarejo AB, Segarra AB, et al. (2014) Brain, heart and kidney correlate for the control of blood pressure and water balance: role of angiotensinases. Neuroendocrinology 100: 198–208.    

3.Prieto I, Segarra AB, Martinez-Canamero M, et al. (2017) Bidirectional asymmetry in the neurovisceral communication for the cardiovascular control: New insights. Endocr Regul 51: 157–167.    

4.Prieto I, Segarra AB, de Gasparo M, et al. (2018) Divergent profile between hypothalamic and plasmatic aminopeptidase activities in WKY and SHR. Influence of beta-adrenergic blockade. Life Sci 192: 9–17.

5.Parati G, Ochoa JE, Lombardi C, et al. (2013) Assessment and management of blood-pressure variability. Nat Rev Cardiol 10: 143–155.    

6.Banegas I, Prieto I, Vives F, et al. (2006) Brain aminopeptidases and hypertension. J Renin Angiotensin Aldosterone Syst 7: 129–134.    

7.Banegas I, Prieto I, Vives F, et al. (2009) Asymmetrical response of aminopeptidase A and nitric oxide in plasma of normotensive and hypertensive rats with experimental hemiparkinsonism. Neuropharmacology 56: 573–579.    

8.Banegas I, Prieto I, Segarra AB, et al. (2011) Blood pressure increased dramatically in hypertensive rats after left hemisphere lesions with 6-hydroxydopamine. Neurosci Lett 500: 148–150.    

9.Banegas I, Prieto I, Segarra AB, et al. (2017) Bilateral distribution of enkephalinase activity in the medial prefrontal cortex differs between WKY and SHR rats unilaterally lesioned with 6-hydroxydopamine. Prog Neuropsychopharmacol Biol Psychiatry 75: 213–218.    

10.Prieto I, Segarra AB, Villarejo AB, et al. (2019) Neuropeptidase activity in the frontal cortex of Wistar-Kyoto and spontaneously hypertensive rats treated with vasoactive drugs: a bilateral study. J Hypertens 37: 612–628.    

11.Cuspidi C, Tadic M, Grassi G, et al. (2018) Mancia G. Treatment of hypertension: The ESH/ESC guidelines recommendations. Pharmacol Res 128: 315–321.

12.Ramírez-Sánchez M, Prieto I, Wangensteen R, et al. (2013) The renin-angiotensin system: new insight into old therapies. Curr Med Chem 20: 1313–1322.    

13.Ferdinand KC, Balavoine F, Besse B, et al. (2019) Efficacy and safety of Firibastat, a first-in-class brain aminopeptidase A inhibitor, in hypertensive overweight patients of multiple ethnic origins: A Phase 2, open-label, multicenter, dose-titrating study. Circulation 140: 138–146.    

14.Gao J, Marc Y, Iturrioz X, et al. (2014) A new strategy for treating hypertension by blocking the activity of the brain renin-angiotensin system with aminopeptidase A inhibitors. Clin Sci (Lond) 127: 135–148.    

15.Keck M, De Almeida H, Compère D, et al. (2019) NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase a inhibitor for treating hypertension. Hypertension 73: 1300–1307.    

16.Wright JW, Mizutani S, Murray CE, et al. (1990) Aminopeptidase-induced elevations and reductions in blood pressure in the spontaneously hypertensive rat. J Hypertens 8: 969–974.    

17.Wright JW, Jensen LL, Cushing LL, et al. (1989) Leucine aminopeptidase M-induced reductions in blood pressure in spontaneously hypertensive rats. Hypertension 13: 910–915.    

18.Zini S, Masdehors P, Lenkei Z, et al. (1997) Aminopeptidase A: distribution in rat brain nuclei and increased activity in spontaneously hypertensive rats. Neuroscience 78: 1187–1193.    

19.Banegas I, Prieto I, Segarra AB, et al. (2017) Study of the neuropeptide function in Parkinson's disease using the 6-Hydroxydopamine model of experimental Hemiparkinsonism. AIMS Neuroscience 4: 223–237.    

20.Kondo K, Ebihara A, Suzuki H, et al. (1981) Role of dopamine in the regulation of blood pressure and the renin--angiotensin-aldosterone system in conscious rats. Clin Sci (Lond) 61: 235s–237s.    

21.Zeng C, Jose PA (2011) Dopamine receptors: important antihypertensive counterbalance against hypertensive factors. Hypertension 57: 11–17.    

22.Förstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33: 829–837.    

23.Calver A, Collier J, Vallance P (1993) Nitric oxide and the control of human vascular tone in health and disease. Eur J Med 2: 48–53.

24.Venturelli M, Pedrinolla A, Boscolo Galazzo I, et al. (2018) Impact of nitric oxide bioavailability on the progressive cerebral and peripheral circulatory impairments during aging and Alzheimer's disease. Front Physiol 9: 169.    

25.Steinert JR, Chernova T, Forsythe ID (2010) Nitric oxide signaling in brain function, dysfunction, and dementia. Neuroscientist 16: 435–452.    

26.Maia-de-Oliveira JP, Trzesniak C, Oliveira IR, et al. (2012) Nitric oxide plasma/serum levels in patients with schizophrenia: a systematic review and meta-analysis. Braz J Psychiatry 34: S149–155.

27.Nakano Y, Yoshimura R, Nakano H, et al. (2010) Association between plasma nitric oxide metabolites levels and negative symptoms of schizophrenia: a pilot study. Hum Psychopharmacol 25: 139–144.    

28.Shabeeh H, Khan S, Jiang B, et al. (2017) Blood pressure in healthy humans is regulated by neuronal no synthase. Hypertension 69: 970–976.    

29.Chen ZQ, Mou RT, Feng DX, et al. (2017) The role of nitric oxide in stroke. Med Gas Res 7: 194–203.    

30.Zheng R, Qin L, Li S, et al. (2014) CT perfusion-derived mean transit time of cortical brain has a negative correlation with the plasma level of nitric oxide after subarachnoid hemorrhage. Acta Neurochir (Wien) 156: 527–533.    

31.Taffi R, Nanetti L, Mazzanti L, et al. (2008) Plasma levels of nitric oxide and stroke outcome. J Neurol 255: 94–98.    

32.Li S, Wang Y, Jiang Z, et al. (2018) Impaired cognitive performance in endothelial nitric oxide synthase knockout mice after ischemic stroke: A pilot study. Am J Phys Med Rehabil 97: 492–499.    

33.Bernard C (1878) Etude sur la physiologie du coeur. La science experimentale: 316–366. Available from: https://gallica.bnf.fr/ark:/12148/bpt6k69992b/f316.image.

34.Thayer JF, Lane RD (2009) Claude Bernard and the heart-brain connection: further elaboration of a model of neurovisceral integration. Neurosci Biobehav Rev 33: 81–88.    

35.Segarra AB, Prieto I, Banegas I, et al. (2012) Asymmetrical effect of captopril on the angiotensinase activity in frontal cortex and plasma of the spontaneously hypertensive rats: expanding the model of neuroendocrine integration. Behav Brain Res 230: 423–427.    

36.Segarra AB, Prieto I, Banegas I, et al. (2013) The brain-heart connection: frontal cortex and left ventricle angiotensinase activities in control and captopril-treated hypertensive rats-a bilateral study. Int J Hypertens 2013: 156179.

37.Segarra AB, Banegas I, Prieto I, et al. (2016) Brain asymmetry and dopamine: beyond motor implications in Parkinson's disease and experimental hemiparkinsonism. Rev Neurol 63: 415–421.

38.de Jager L, Amorim EDT, Lucchetti BFC, et al. (2018) Nitric oxide alterations in cardiovascular system of rats with Parkinsonism induced by 6-OHDA and submitted to previous exercise. Life Sci 204: 78–86.    

39.Alexander N, Kaneda N, Ishii A, et al. (1990) Right-left asymmetry of tyrosine hydroxylase in rat median eminence: influence of arterial baroreflex nerves. Brain Res 523: 195–198.    

40.Hersh LB (1985) Characterization of membrane-bound aminopeptidases from rat brain:identification of the enkephalin-degrading aminopeptidase. J Neurochem 44: 1427–1435.    

41.Wright JW, Harding JW (1997) Important roles for angiotensin III and IV in the brain renin-angiotensin system. Brain Res Rev 25: 96–124.    

© 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Article outline

Show full outline
Copyright © AIMS Press All Rights Reserved