{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:37:28Z","timestamp":1760150248736,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministry of Science and Innovation","doi-asserted-by":"publisher","award":["SAF 2008 04685 C02 01"],"award-info":[{"award-number":["SAF 2008 04685 C02 01"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It has been suggested that the neuro-visceral integration works asymmetrically and that this asymmetry is dynamic and modifiable by physio-pathological influences. Aminopeptidases of the renin\u2013angiotensin system (angiotensinases) have been shown to be modifiable under such conditions. This article analyzes the interactions of these angiotensinases between the left or right frontal cortex (FC) and the same enzymes in the hypothalamus (HT), pituitary (PT), adrenal (AD) axis (HPA) in control spontaneously hypertensive rats (SHR), in SHR treated with a hypotensive agent in the form of captopril (an angiotensin-converting enzyme inhibitor), and in SHR treated with a hypertensive agent in the form of the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). In the control SHR, there were significant negative correlations between the right FC with HPA and positive correlations between the left FC and HPA. In the captopril group, the predominance of negative correlations between the right FC and HPA and positive correlations between the HPA and left FC was maintained. In the L-NAME group, a radical change in all types of interactions was observed; particularly, there was an inversion in the predominance of negative correlations between the HPA and left FC. These results indicated a better balance of neuro-visceral interactions after captopril treatment and an increase in these interactions in the hypertensive animals, especially in those treated with L-NAME.<\/jats:p>","DOI":"10.3390\/ijms242116007","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T08:15:56Z","timestamp":1699258556000},"page":"16007","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Correlational Study of Aminopeptidase Activities between Left or Right Frontal Cortex versus the Hypothalamus, Pituitary, Adrenal Axis of Spontaneously Hypertensive Rats Treated with Hypotensive or Hypertensive Agents"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0624-9504","authenticated-orcid":false,"given":"Isabel","family":"Prieto","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9409-6052","authenticated-orcid":false,"given":"Ana Bel\u00e9n","family":"Segarra","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1910-3726","authenticated-orcid":false,"given":"Inmaculada","family":"Banegas","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3241-0066","authenticated-orcid":false,"given":"Magdalena","family":"Mart\u00ednez-Ca\u00f1amero","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-8968","authenticated-orcid":false,"given":"Raquel","family":"Dur\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Vives","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-9148","authenticated-orcid":false,"given":"Germ\u00e1n","family":"Dom\u00ednguez-V\u00edas","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences, Ceuta Campus, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Ram\u00edrez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1136\/hrt.76.3_Suppl_3.7","article-title":"The renin-angiotensin system and the heart: A historical review","volume":"76","author":"Cleland","year":"1996","journal-title":"Heart"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.regpep.2007.03.006","article-title":"Enzymatic pathways of the brain renin-angiotensin system: Unsolved problems and continuing challenges","volume":"143","author":"Karamyan","year":"2007","journal-title":"Regul. Pept."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.neubiorev.2017.02.003","article-title":"The hierarchical basis of neurovisceral integration","volume":"75","author":"Smith","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0278-2626(03)00011-3","article-title":"Central and autonomic nervous system integration in emotion","volume":"52","author":"Hagemann","year":"2003","journal-title":"Brain Cogn."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.biopha.2017.07.091","article-title":"Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies","volume":"94","author":"Patel","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jackson, L., Eldahshan, W., Fagan, S.C., and Ergul, A. (2018). Within the Brain: The Renin Angiotensin System. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030876"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1097\/HJH.0b013e3282f5ed58","article-title":"Brain and peripheral angiotensin II type 1 receptors mediate renal vasoconstrictor and blood pressure responses to angiotensin IV in the rat","volume":"26","author":"Yang","year":"2008","journal-title":"J. Hypertens."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1358\/dnp.2009.22.3.1325032","article-title":"Targeting the insulin-regulated aminopeptidase\/AT4 receptor for cognitive disorders","volume":"22","author":"Hallberg","year":"2009","journal-title":"Drug News Perspect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.regpep.2003.12.010","article-title":"Effects of des-aspartate-angiotensin I on the actions of angiotensin III in the renal and mesenteric vasculature of normo- and hypertensive rats","volume":"120","author":"Mustafa","year":"2004","journal-title":"Regul. Pept."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1016\/0014-2999(94)90714-5","article-title":"Novel central action of des-Asp-angiotensin I","volume":"257","author":"Sim","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0014-2999(95)00686-9","article-title":"Actions of D-amino acid-substituted analogues of des-Asp-angiotensin I on the central pressor action of angiotensin III","volume":"294","author":"Radhakrishnan","year":"1995","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1124\/mol.120.119388","article-title":"Five Decades of Research on Opioid Peptides: Current Knowledge and Unanswered Questions","volume":"98","author":"Fricker","year":"2020","journal-title":"Mol. Pharmacol."},{"key":"ref_13","first-page":"625","article-title":"Neuropeptidases","volume":"Volume 7","author":"Lajtha","year":"2007","journal-title":"Handbook of Neurochemistry and Molecular Neurobiology: Neural Protein Metabolism and Function"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1097\/HJH.0000000000001884","article-title":"Neuropeptidase activity in the frontal cortex of Wistar-Kyoto and spontaneously hypertensive rats treated with vasoactive drugs: A bilateral study","volume":"37","author":"Prieto","year":"2019","journal-title":"J. Hypertens."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1159\/000368835","article-title":"Brain, heart and kidney correlate for the control of blood pressure and water balance: Role of angiotensinases","volume":"100","author":"Prieto","year":"2014","journal-title":"Neuroendocrinology"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Segarra, A.B., Prieto, I., Banegas, I., Mart\u00ednez-Ca\u00f1amero, M., Villarejo, A.B., Dom\u00ednguez-V\u00edas, G., de Gasparo, M., and Ram\u00edrez-S\u00e1nchez, M. (2021). Interaction between Angiotensinase Activities in Pituitary and Adrenal Glands of Wistar-Kyoto and Spontaneously Hypertensive Rats under Hypotensive or Hypertensive Treatments. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157823"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1161\/01.HYP.26.4.691","article-title":"Sympathetically mediated hypertension caused by chronic inhibition of nitric oxide","volume":"26","author":"Sander","year":"1995","journal-title":"Hypertension"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.bbr.2012.02.039","article-title":"Asymmetrical effect of captopril on the angiotensinase activity in frontal cortex and plasma of the spontaneously hypertensive rats: Expanding the model of neuroendocrine integration","volume":"230","author":"Segarra","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"156179","DOI":"10.1155\/2013\/156179","article-title":"The brain-heart connection: Frontal cortex and left ventricle angiotensinase activities in control and captopril-treated hypertensive rats\u2014A bilateral study","volume":"2013","author":"Segarra","year":"2013","journal-title":"Int. J. Hypertens"},{"key":"ref_20","unstructured":"Stuss, D.T., and Knight, R.T. (2002). Oxford University Press."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/gbb.12191","article-title":"Behavioral flexibility in rats and mice: Contributions of distinct frontocortical regions","volume":"14","author":"Hamilton","year":"2015","journal-title":"Genes Brain Behav."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s00702-023-02610-z","article-title":"Hemispheric asymmetries in mental disorders: Evidence from rodent studies","volume":"130","author":"Mundorf","year":"2023","journal-title":"J. Neural Transm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/psyp.12332","article-title":"Autonomic responses to lateralized cold pressor and facial cooling tasks","volume":"52","author":"McGinley","year":"2015","journal-title":"Psychophysiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1023\/B:NEUR.0000021910.65920.41","article-title":"The number, size, and type of axons in rat subcortical white matter on left and right sides: A stereological, ultrastructural study","volume":"32","author":"Partadiredja","year":"2003","journal-title":"J. Neurocytol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.npep.2009.12.016","article-title":"Correlations between angiotensinase activity asymmetries in the brain and paw preference in rats","volume":"44","author":"Wu","year":"2010","journal-title":"Neuropeptides"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/hipo.20727","article-title":"Proteomics reveal rat hippocampal lateral asymmetry","volume":"21","author":"Samara","year":"2011","journal-title":"Hippocampus"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"995","DOI":"10.2174\/1871527315666160527155014","article-title":"Neuroinflammatory Markers in Spontaneously Hypertensive Rat Brain: An Immunohistochemical Study","volume":"15","author":"Tayebati","year":"2016","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100424","DOI":"10.1016\/j.mcpro.2022.100424","article-title":"Soluble ANPEP Released from Human Astrocytes as a Positive Regulator of Microglial Activation and Neuroinflammation: Brain Renin-Angiotensin System in Astrocyte-Microglia Crosstalk","volume":"21","author":"Kim","year":"2022","journal-title":"Mol. Cell Proteom. MCP"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1161\/01.HYP.36.2.259","article-title":"Angiotensin in the nucleus tractus solitarii contributes to neurogenic hypertension caused by chronic nitric oxide synthase inhibition","volume":"36","author":"Eshima","year":"2000","journal-title":"Hypertension"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ejphar.2007.05.060","article-title":"Vascular effects of long-term propranolol administration after chronic nitric oxide blockade","volume":"571","author":"Priviero","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kiss, D.S., Toth, I., Jocsak, G., Barany, Z., Bartha, T., Frenyo, L.V., Horvath, T.L., and Zsarnovszky, A. (2020). Functional Aspects of Hypothalamic Asymmetry. Brain Sci., 10.","DOI":"10.3390\/brainsci10060389"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.biopsycho.2008.11.002","article-title":"Circadian and seasonal variability of resting frontal EEG asymmetry","volume":"80","author":"Peterson","year":"2009","journal-title":"Biol. Psychol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/0741-5214(94)90004-3","article-title":"Expansion of aortic aneurysms is reduced by propranolol in a hypertensive rat model","volume":"20","author":"Slaiby","year":"1994","journal-title":"J. Vasc. Surg."},{"key":"ref_34","unstructured":"Paxinos, G., and Watson, C. (1998). The Rat Brain in Stereotaxic Coordinates, Academic Press. [4th ed.]."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/0006-291X(62)90029-3","article-title":"Fluorimetric measurement of alkaline phosphatase and aminopeptidase activities in the order of 10\u201314 mole","volume":"9","author":"Greenberg","year":"1962","journal-title":"Biochem. Biophys. Res Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/0005-2744(80)90100-X","article-title":"Purification by affinity chromatography using amastatin and properties of aminopeptidase A from pig kidney","volume":"613","author":"Tobe","year":"1980","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/16007\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:18:13Z","timestamp":1760131093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/16007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,6]]},"references-count":37,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242116007"],"URL":"https:\/\/doi.org\/10.3390\/ijms242116007","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,11,6]]}}}