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dc.contributor.authorLeenen, F.H.H.
dc.contributor.authorBlaustein, M.P.
dc.contributor.authorHamlyn, J.M.
dc.date.accessioned2019-07-15T16:12:14Z
dc.date.available2019-07-15T16:12:14Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85031293134&doi=10.1530%2fEC-17-0161&partnerID=40&md5=92813d854af73d490ec20d3c09a0706a
dc.identifier.urihttp://hdl.handle.net/10713/9958
dc.description.abstractIn the brain, angiotensinergic pathways play a major role in chronic regulation of cardiovascular and electrolyte homeostasis. Increases in plasma angiotensin II (Ang II), aldosterone, [Na+] and cytokines can directly activate these pathways. Chronically, these stimuli also activate a slow neuromodulatory pathway involving local aldosterone, mineralocorticoid receptors (MRs), epithelial sodium channels and endogenous ouabain (EO). This pathway increases AT1R and NADPH oxidase subunits and maintains/further increases the activity of angiotensinergic pathways. These brain pathways not only increase the setpoint of sympathetic activity per se, but also enhance its effectiveness by increasing plasma EO and EO-dependent reprogramming of arterial and cardiac function. Blockade of any step in this slow pathway or of AT1R prevents Ang II-, aldosterone- or salt and renal injury-induced forms of hypertension. MR/AT1R activation in the CNS also contributes to the activation of sympathetic activity, the circulatory and cardiac RAAS and increase in circulating cytokines in HF post MI. Chronic central infusion of an aldosterone synthase inhibitor, MR blocker or AT1R blocker prevents a major part of the structural remodeling of the heart and the decrease in LV function post MI, indicating that MR activation in the CNS post MI depends on aldosterone, locally produced in the CNS. Thus, Ang II, aldosterone and EO are not simply circulating hormones that act on the CNS but rather they are also paracrine neurohormones, locally produced in the CNS, that exert powerful effects in key CNS pathways involved in the long-term control of sympathetic and neuro-endocrine function and cardiovascular homeostasis. Copyright 2017 The authors.en_US
dc.description.sponsorshipResearch from the authors reviewed in this article was supported by operating grants from the Canadian Institutes of Health Research and Quantum Genomics, Paris, France (for FL), and from the American Heart Association (for MB).en_US
dc.description.urihttps://www.doi.org/10.1530/EC-17-0161en_US
dc.language.isoen_USen_US
dc.publisherBioScientifica Ltd.en_US
dc.relation.ispartofEndocrine Connections
dc.subjectAldosteroneen_US
dc.subjectAngiotensin IIen_US
dc.subjectCNS regulationen_US
dc.subjectEndogenous ouabainen_US
dc.subjectNeurohormonesen_US
dc.titleUpdate on angiotensin II: New endocrine connections between the brain, adrenal glands and the cardiovascular systemen_US
dc.typeArticleen_US
dc.identifier.doi10.1530/EC-17-0161


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