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111 Physiology, Biochemistry and Pharmacology 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. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its version of June 24, 1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1988 Printed in Germany The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant pro- tective laws and regulations and therefore free for general use. Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. 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
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