International Journal of Hypertension Brain RAS: Hypertension and Beyond Guest Editors: Marc de Gasparo, Robert C. Speth, Ovidiu C. Baltatu, and Patrick Vanderheyden Brain RAS: Hypertension and Beyond International Journal of Hypertension Brain RAS: Hypertension and Beyond Guest Editors: Marc de Gasparo, Robert C. Speth, Ovidiu C. Baltatu, and Patrick Vanderheyden Copyright © 2013 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “International Journal of Hypertension.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board Maciej Banach, Poland Kazuomi Kario, Japan Gary Lee Schwartz, USA Vecihi Batuman, USA Tomohiro Katsuya, Japan Joseph I. Shapiro, USA Claudio Borghi, Italy Marcel Lebel, Canada Helmy M. Siragy, USA Vito M. Campese, USA Kiyoshi Matsumura, Japan Masayoshi Soma, Japan Francesco Cappuccio, UK Albert Mimran, France Thomas Unger, Germany Oscar A. Carretero, USA Shawna D. Nesbitt, USA Franco Veglio, Italy Santina Cottone, Italy G. Parati, Italy M. Volpe, Italy Daniel Duprez, USA Stefano Perlini, Italy B. Waeber, Switzerland Csaba Farsang, Hungary Roberto Pontremoli, Italy Donna Wang, USA John M. Flack, USA Hiromi Rakugi, Japan M. R. Weir, USA J. Hall, USA Giuseppe Schillaci, Italy Yoram Yagil, Israel Junichiro Hashimoto, Japan Markus Schlaich, Australia Xiao-Ping Yang, USA Contents Brain RAS: Hypertension and Beyond,MarcdeGasparo,RobertC.Speth,OvidiuC.Baltatu, and Patrick Vanderheyden Volume 2013, Article ID 157180, 3 pages Immunohistochemical Localization of AT1a,AT1b, and AT2 Angiotensin II Receptor Subtypes in the Rat Adrenal, Pituitary, and Brain with a Perspective Commentary, Courtney Premer, Courtney Lamondin, Ann Mitzey, Robert C. Speth, and Mark S. Brownfield Volume 2013, Article ID 175428, 22 pages Distinct Molecular Effects of Angiotensin II and Angiotensin III in Rat Astrocytes, Michelle A. Clark, Chinh Nguyen, and Hieu Tran Volume 2013, Article ID 782861, 8 pages The Brain-Heart Connection: Frontal Cortex and Left Ventricle Angiotensinase Activities in Control and Captopril-Treated Hypertensive Rats—A Bilateral Study, Ana B. Segarra, Isabel Prieto, Inmaculada Banegas, Ana B. Villarejo, Rosemary Wangensteen, Marc de Gasparo, Francisco Vives, and Manuel Ram´ırez-Sanchez´ Volume 2013, Article ID 156179, 7 pages Elevated Blood Pressure in the Acute Phase of Stroke and the Role of Angiotensin Receptor Blockers, Simona Lattanzi, Mauro Silvestrini, and Leandro Provinciali Volume 2013, Article ID 941783, 8 pages AT2 Receptor-Interacting Proteins ATIPs in the Brain, Sylvie Rodrigues-Ferreira, Erwann le Rouzic, Traci Pawlowski, Anand Srivastava, Florence Margottin-Goguet, and Clara Nahmias Volume 2013, Article ID 513047, 6 pages The Brain Renin-Angiotensin System and Mitochondrial Function: Influence on Blood Pressure and Baroreflex in Transgenic Rat Strains, Manisha Nautiyal, Amy C. Arnold, Mark C. Chappell, and Debra I. Diz Volume 2013, Article ID 136028, 8 pages The Angiotensin-Melatonin Axis, Luciana A. Campos, Jose Cipolla-Neto, Fernanda G. Amaral, Lisete C. Michelini, Michael Bader, and Ovidiu C. Baltatu Volume 2013, Article ID 521783, 7 pages RAS in Pregnancy and Preeclampsia and Eclampsia, M. Rodriguez, J. Moreno, and J. Hasbun Volume 2012, Article ID 739274, 6 pages The Angiotensin II Type 2 Receptor in Brain Functions: An Update, Marie-Odile Guimond and Nicole Gallo-Payet Volume 2012, Article ID 351758, 18 pages The Prorenin and (Pro)renin Receptor: New Players in the Brain Renin-Angiotensin System?, Wencheng Li, Hua Peng, Dale M. Seth, and Yumei Feng Volume 2012, Article ID 290635, 8 pages Upregulation of the Renin-Angiotensin-Aldosterone-Ouabain System in the Brain Is the Core Mechanism in the Genesis of All Types of Hypertension, Hakuo Takahashi Volume 2012, Article ID 242786, 10 pages Roles of Brain Angiotensin II in Cognitive Function and Dementia, Masaki Mogi, Jun Iwanami, and Masatsugu Horiuchi Volume 2012, Article ID 169649, 7 pages Discovery of Inhibitors of Insulin-Regulated Aminopeptidase as Cognitive Enhancers, Hanna Andersson and Mathias Hallberg Volume 2012, Article ID 789671, 18 pages Renin-Angiotensin System and Sympathetic Neurotransmitter Release in the Central Nervous System of Hypertension, Kazushi Tsuda Volume 2012, Article ID 474870, 11 pages Cardiac-Autonomic Imbalance and Baroreflex Dysfunction in the Renovascular Angiotensin-Dependent Hypertensive Mouse, Bianca P. Campagnaro, Agata L. Gava, Silvana S. Meyrelles, and Elisardo C. Vasquez Volume 2012, Article ID 968123, 9 pages Hindawi Publishing Corporation International Journal of Hypertension Volume 2013, Article ID 157180, 3 pages http://dx.doi.org/10.1155/2013/157180 Editorial Brain RAS: Hypertension and Beyond Marc de Gasparo,1 Robert C. Speth,2 Ovidiu C. Baltatu,3 and Patrick Vanderheyden4 1 Unit of Physiology, University of Jaen,´ 23071 Jaen,´ Spain 2 Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328-2018, USA 3 Center of Biomedical Engineering, University Camilo Castelo Branco, 12247-004 Sao˜ Jose´ dos Campos, SP, Brazil 4 Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, 1050 Brussels, Belgium Correspondence should be addressed to Marc de Gasparo; m.de [email protected] Received 25 February 2013; Accepted 25 February 2013 Copyright © 2013 Marc de Gasparo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cardiac output and vascular resistance are the cornerstones of paraventricular, and solitary tract nucleus of the rat brain as blood pressure regulation, which is achieved through neural, well as in the pituitary and adrenal. humoral, and local tissue factors. Ang II formation in the pineal gland and glial cells The sympathetic nervous system (SNS) and the renin- appears to depend on alternative pathways including chy- angiotensin system (RAS) play a major role in the control mase (L. A. Campos et al.). One possibility might be that of blood pressure. Angiotensins act as endocrine, paracrine, the prorenin receptor (PRR) binds prorenin or renin from and autocrine regulators. The peripheral physiological and circulationtoformAngIandchymasetoformAngII. pathophysiological actions of the RAS are well established. The brain PRR appears to initiate the brain angiotensin The existence and functional relevance of the RAS inthe peptide formation (W. Li et al.). Indeed, PRR is expressed brainisincreasinglyrecognizedasamajorregulatorofthe ubiquitously in the brain with the highest expression levels cardiovascular (CV) system and a significant drug target in the pituitary and frontal lobe. Recent findings indicate that for antihypertensive and other CV therapeutics. All the PRR has RAS independent roles associated with the vacuolar constituentsoftheRASoccurinthebrainandparticipate proton-ATPase and the Wnt signaling pathways (W.Li et al.). in the regulation of blood pressure through sympathetic PRRinthebraincouldplayapivotalroleinneuralregulation activation and vasopressin release. In addition, an intercon- of blood pressure and body fluid homeostasis. nection between neurotransmitters and the brain RAS affects In addition, AT4/IRAP and Mas receptors are also present behavior and neurological diseases, for example, Parkinson’s, in the brain. Aminopeptidases (and other angiotensins and Alzheimer’s diseases. Moreover, the clinical efficacy of degrading enzymes, e.g., ACE2 and endopeptidase), which renin and ACE inhibitors and angiotensin receptor blockers form fragments such as Ang III, Ang IV, Ang 2–10, Ang 1–9, (ARBs) and the presence of their targets in the brain illustrate and Ang 1–7, are also the topic of several reports (A. B. Segarra the synergistic interaction between brain and peripheral RAS. et al.; M. A. Clark et al.). This special issue illustrates some aspects of the brain RAS Formation of Ang III in the brain may promote hyper- pathway and function including its effect on the circadian tension while Ang IV, which inhibits vasopressinase activity rhythm of blood pressure. and may have a therapeutic value for cognitive function in the The RAS has been described in the brain. Using sub- brain. type specific antibodies, C. Premer et al. observed selective There is still a debate regarding the relative importance of expression of AT1a, AT1b, and AT2 receptor subtypes in Ang II and Ang III in the brain. Using astrocytes in culture neurons and glia in a large number of brain regions including andaninhibitorofaminopeptidaseAtopreventconversion the subfornical organ, median eminence, area postrema, of Ang II to Ang III, M. A. Clark et al. demonstrate that both 2 International Journal of Hypertension Ang II and Ang III induce phosphorylation of MAPK and and dementia (M. Mogi et al.). In addition, the AT2 receptor JNK and stimulate astrocyte growth equipotently. appears to play a role in metabolic syndrome as it regulates Ang IV binds to the AT4 receptor. While the AT4 receptor appetite and increases glucose uptake. Finally, it is proposed has been convincingly shown to be the insulin-regulated that the AT2 receptor behaves like a gate keeper of cellular and aminopeptidase IRAP, (also known as vasopressinase and tissue homeostasis (M. O. Guimond