Reviews of 111 Physiology, Biochemistry and Pharmacology Editors M. P. Blaustein, Baltimore • H. Grunicke, Innsbruck E. Habermann, Giel3en • H. Neurath, Seattle S. Numa, Kyoto • D. Pette, Konstanz B. Sakmann, G6ttingen • U. Trendelenburg, Wiirzburg K.J. Ullrich, Frankfurt/M With 32 Figures and 10 Tables Springer-Verlag Berlin Heidelberg New York London Paris Tokyo ISBN 3-540-19156-9 Springer-Verlag Berlin Heidelberg NewYork 1SBN 0-387-19156-9 Springer-Verlag NewYork Berlin Heidelberg Library of Congress-Catalog-Card Number 74-3674 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. 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Typesetting:K+ V Fotosatz, Beerfelden Offsetprinting and Binding: Konrad Triltsch, D-8700 W~rzburg 2127/3130-543210- Printed on acid-free paper Contents Regulation of Blood Pressure by Central Neuro- transmitters and Neuropeptides By A. PHILIVPU, Innsbruck, Austria With 8 Figures and 9 Tables ............... The Roles of Calcium and Phosphoinositides in the Mechanisms of al-Adrenergic and Other Agonists By J. H. EXTON, Nashville, Tennessee, USA With 24 Figures and 1 Table ............... 117 Subject Index ................................ 225 Indexed in Current Contents Rev. Physiol. Biochem. Pharmacol., Vol. 111 © Springer-Verlag 1988 Regulation of Blood Pressure by Central Neurotransmitters and Neuropeptides* ATHINEOS PHILIPPU Contents I Introduction ............................................................. 3 2 Functional Significance of Neuronal Pathways in Blood Pressure Regulation ..... 4 3 Catecholamines .......................................................... 5 3.1 Mapping of Catecholamine-Containing Neurons ....................... 5 3.1.1 Brainstem ......................................................... 6 3.t.2 Hypothalamus ..................................................... 9 3.2 Cardiovascular Effects of Catecholamines and Related Drugs ............ 9 3.2.1 Cerebroventricular System ........................................... 9 3.2.2 Brainstem ......................................................... 11 3.2.3 Hypothalamus ..................................................... 22 3.3 Catecholamines in Experimental and Genetic Hypertension .............. 29 3.4 Possible Mechanisms of Clonidine Action ............................. 39 4 Serotonin ............................................................... 43 4.1 Mapping of Serotonin-Containing Neurons ............................ 43 4.2 Cardiovascular Effects of Serotonin and Related Drugs ................. 44 4.2.1 Cerebroventricular System ........................................... 44 4.2.2 Raphe Nuclei ...................................................... 45 4.3 Serotonin in Drug-Induced Hypotension, and in Experimental and Genetic Hypertension ...................................................... 46 5 Histamine ............................................................... 47 5.1 Mapping of Histamine-Containing Neurons ........................... 47 5.2 Cardiovascular Effects of Centrally Administered Histamine ............. 47 5.3 Histamine in Genetic Hypertension ................................... 50 6 GABA and Other Neuroinhibitory and Neuroexcitatory Amino Acids ........... 51 6.1 Mapping of Amino Acid-Containing Neurons .......................... 51 6.2 Cardiovascular Effects of Amino Acids and Related Drugs .............. 52 6.2.1 Cerebroventricular System ........................................... 52 6.2.2 Brainstem ......................................................... 53 6.2.3 Hypothalamus ..................................................... 56 6.3 GABA in Genetic Hypertension ...................................... 57 Institut for Pharmakodynamik und Toxikologie der Universit~t Innsbruck, Peter-Mayr-Str. 1, A-6020 Innsbruck, Austria * Work carried out by the author and his co-workers was supported by the Deutsche Forschungsgemeinschaft and the Fonds zur FOrderung der Wissenschaftlichen Forschung. 2 A. Philippu 7 Acetylcholine ............................................................ 57 7.1 Mapping of Acetylcholine-Containing Neurons ......................... 57 7.2 Cardiovascular Effects of Acetylcholine and Related Drugs .............. 57 7.2.1 Cerebroventricular System ........................................... 57 7.2.2 Brainstem ......................................................... 59 7.2.3 Hypothalamus ..................................................... 6O 7.3 Acetylcholine in Drug-Induced Hypotension and in Experimental and Genetic Hypertension ............................................... 62 8 Vasopressin .............................................................. 63 8.1 Mapping of Vasopressin-Containing Neurons .......................... 63 8.2 Cardiovascular Effects of Vasopressin and Related Drugs ................ 63 8.2.1 Cerebroventricular System ........................................... 63 8.2.2 Brainstem ......................................................... 64 8.2.3 Hypothalamus ..................................................... 65 8.3 Vasopressin in Experimental and Genetic Hypertension ................. 66 9 Angiotensin.............................................................. 66 9.1 Mapping of Angiotensin-Containing Neurons .......................... 66 9.2 Cardiovascular Effects of Angiotensin and Related Drugs ............... 67 92.1 Cerebroventricular System ........................................... 67 9.2.2 Brainstem ......................................................... 67 9.2.3 Hypothalamus ..................................................... 68 9.3 Angiotensin in Experimental and Genetic Hypertension ................. 69 10 Opioids ................................................................. 69 t 0.1 Mapping of Opioid-Containing Neurons .............................. 69 10.2 Cardiovascular Effects of Opioids and Related Drugs ................... 70 10.2.1 Cerebroventricular System ........................................... 70 10.2.2 Brainstem ......................................................... 72 i 0.2.3 Hypothalamus ..................................................... 73 10.3 Opioids in Genetic Hypertension ..................................... 74 I1 Substance P ............................................................. 74 11.1 Mapping of Substance P-Containing Neurons .......................... 74 11.2 Cardiovascular Effects of Substance P and Related Drugs ............... 75 11.2.t Cerebroventricular System ........................................... 75 11.2.2 Brainstem ......................................................... 75 12 Neuropeptide Y .......................................................... 76 12.1 Mapping of Neuropeptide Y-Containing Neurons ....................... 76 12.2 Cardiovascular Effects of Centrally Applied Neuropeptide Y ............. 77 12.3 Neuropeptide Y in Experimental and Genetic Hypertension .............. 78 13 Neurotensin ............................................................. 78 13.1 Mapping of Neurotensin-Containing Neurons .......................... 78 13.2 Cardiovascular Effects of Centrally Applied Neurotensin ................ 78 14 Atrial Natriuretic Factor .................................................. 79 14.1 Mapping of Atrial Natriuretic Factor-Containing Neurons ............... 79 14.2 Cardiovascular Effects of Centrally Applied Atrial Natriuretic Factor; Atrial Natriuretic Factor in Genetic Hypertension ...................... 79 15 General Conclusions ...................................................... 80 15.1 Brainstem ......................................................... 80 15.2 Hypothalamus ..................................................... 81 t 5.3 Hypertension ...................................................... 81 References .................................................................. 83 Regulation of Blood Pressure by Central Neurotransmitters and Neuropeptides 3 1 Introduction The central regulation of arterial blood pressure has been extensively in- vestigated in recent decades. The techniques which have been used include the following: 1. Investigations on the effects of centrally applied agonists and antagonists on blood pressure, as well as on blood pressure changes elicited by stimula- tion of distinct brain areas 2. The identification of neurons by fluorescence microscopy and immuno- chemistry in discrete brain areas involved in blood pressure regulation 3. Determination of the levels of neurotransmitters and neuropeptides and of the