The Juxtaglomerular Apparatus: Structure and Function

308 Pages·1989·14.6 MB·English

by  Prof. Dr. med. Roland Taugner

Roland Taugner • Eberhard Hackenthal
The
Juxtaglomerular
Apparatus
Structure and Function
With a contribution on the pathology
of the human JGA by R. Waldherr
With 129 Figures
Springer-Verlag Berlin Heidelberg GmbH
Prof. Dr. med. Roland Taugner
1. Physiologisches Institut der Universităt Heidelberg
Im Neuenheimer Feld 326
6900 Heidelberg, FRG
Prof. Dr. med. Eberhard Hackenthal
Pharmakologisches Institut der Universităt Heidelberg
Im Neuenheimer Feld 366
6900 Heidelberg, FRG
ISBN 978-3-642-88428-3
Library of Congress Cataloging-in-Publication Data
Taugner, Roland. The juxtaglomerular apparatus : structure and function / Roland Taugner, Eberhard Hackenthal ;
with a contribution on the pathology ofthe human JGA 1 by R. Waldherr. Bibliography: lncludes index.
1. Juxtaglomerular apparatus - Physiology. 2. Juxtaglomerular apparatus - Pathophysiologv.
ISBN 978-3-642-88428-3 ISBN 978-3-642-88426-9 (eBook)
DOI 10.1007/978-3-642-88426-9
I. Hackenthal, Eberhard. Il. Waldherr, R. (Riidiger) III. Title. QP249.T38 1989 612'.463 - dc19
This work is subject to copyright. AII rights are reserved, whether the whole or part of the material is concemed, specifically
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paid. Violations fali under the prosecution act of the German Copyright Law.
© Springer-Verlag Berlin Heidelberg 1989
Originally published by Springer-V erlag Berlin Heidelberg New York in 1989
Softcover reprint ofthe hardcover lst edition 1989
The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the ab
sence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore
free for general use.
2127/3145-543210 Printed on acid-free paper
Preface
Until recently it was possible and appropriate to condense and integrate the body of data
available on the juxtaglomerular apparatus (JGA) into the form of conventional reviews.
Indeed, many excellent reviews covering various aspects of the JGA have monitored
the progress made in this field during the last 50 years (e.g. GooRMAGHTIGH 1942, 1945a;
TOBIAN 1960a; REALE et al. 1963; HARTROFT 1966; HATT 1967; VANDER 1967; FAARUP
1971; KAZIMIERCZAK 1971; ROULLER and 0RCI 1971; LATTA 1973; THURAU and MASON
1974; DAVIS and FREEMAN 1976; GoRGAS 1978). In particular, the reviews and updates by
BARAJAS (BARAJAS 1972, 1979, 1981; BARAJAS and POWERS 1984) provided continuous state
of-the-art information on both the structure and the function of the JGA. However, as a
consequence of the development of new techniques in immunocytochemistry, biochemistry,
and molecular biology in the last decade, this flow of information on the renin-angiotensin
system and the JGA has swelled into a flood. This large volume of data is not only
overwhelming by its quantity, but also carries with it several new aspects of broader interest,
such as general questions of cell differentiation and adaptation, structural and biochemical
mechanisms of the secretory process, and integrated control mechanisms of secretion. Fur
thermore, the recognition that the renin-angiot~nsin system plays an important role in the
maintenance of blood pressure and the development of hypertension, the widespread clini
cal use of inhibitors of angiotensin-converting enzyme, and the development of potent in
hibitors of human renin with therapeutic potential have stimulated general interest in all
aspects of the renin-angiotensin system.
Therefore we felt it timely to attempt a comprehensive overview on the present state of
research on the JGA and, in order to accomodate as much of the essential original informa
tion as possible, we have chosen the form of a monograph. In keeping with the longstand
ing cooperation between the authors, a central aim in this enterprise has been the close inte
gration of the description of JGA structure and function.
Nevertheless, structural and functional aspects received a somewhat different treatment
with respect to the completeness of coverage of the literature. The reason for this apparent
inconsistency lies in the fact that the knowledge of JGA morphology is far more advanced
than that of JGA function, whilst at the same time, it is documented in a much smaller
number of publications. Therefore, coverage of the literature on the morphology is more
complete, whereas in the description of functional aspects a more selective approach to
the literature was necessary. Obviously, some personal bias is unavoidable in this proce
dure, and we apologize to all those whose valuable contributions have not been cited. A
subjective view is also inherent to our interpretion of new data which have not yet been
accepted unequivocally as "standard" knowledge and may need further confirmation.
We hope for the kind understanding of the reader if he or she does not agree with our
views.
Two authors cannot give birth to such a monograph without significant help from others
and, first of all, we wish to thank Dr. R.WA LDHERR who contributed the chapter on the
"Pathology of the human juxtaglomerular apparatus", which we feel is an excellent descrip
tion of the topic and fits well into the general line of argumentation from the preceding
nonclinical chapters.
VI Preface
We also thank Dr. KARIN GoRGAS, as well as Drs. J.A.CHRISTENSEN, L.RosiVALL, and
C. P. BOHRLE for critical reading of individual chapters and helpful suggestions for the
preparation of the text. Our own work, as presented in this monograph, originated from the
collaboration with many scientists whose names appear in the text and in the cited refer
ences and will therefore not be listed here. However, we wish to express our gratitude to
Mrs. G. REB, Mrs. M. HARLACHER, Mr. H. WREDE, and Mr. G. RoHS for their valuable tech
nical assistance for many years and to Mrs. M. WYBRANIEC and Mrs. S. RENFRO-KoHL for
their assistance in preparing the manuscript. Our special appreciation is due Mrs. R. HACK
ENTHAL, who not only accompanied our experimental work by expert and unexhaustable
laboratory assistance, but who also took on the burden of collecting, checking, and organiz
ing some 1800 references, as well as typing and editing a large part of the manuscript.
Finally, we wish to thank Springer-Verlag, especially Dr. J. WIECZOREK, and K. RAu for
their efficient and sensitive cooperation and the excellent layout of the book.
Heidelberg, January 1989 R.TAUGNER
E. HACKENTHAL
Table of Contents
Chapter 1 The Juxtaglomerular Apparatus - History of a Concept............................ 1
Chapter 2 Morphology of the Juxtaglomerular Apparatus ........................................... 5
2.1 Components and Definitions ................................................................ 5
2.2 Afferent Arteriole..................................................................................... 7
2.2.1 Overview ............................................................................................... 7
2.2.2 Media Cells of the Afferent Arteriole.............................................. 9
2.2.3 Morphological Prerequisites for Vasoconstriction
in the Renin-Positive and Renin-Negative Portions
of the Afferent Arteriole..................................................................... 14
2.2.4 Additional Aspects of the Functional Morphology of the
Proximal and Distal Portions of the Afferent Arteriole............... 15
2.3 Efferent Arteriole..................................................................................... 17
2.4 Goormaghtigh Cell Field ....................................................................... 20
2.5 Macula Densa .......................................................................................... 25
2.6 Areas of Close Proximity Between Components
of the Juxtaglomerular Apparatus........................................................ 30
2.7 Gap Junction Coupling Between Cells
of the Juxtaglomerular Apparatus........................................................ 33
2.8 Tight Junction Barriers in the Region
of the Juxtaglomerular Apparatus........................................................ 41
Chapter 3 Elements with Structural and/or Functional Relationships
to the Juxtaglomerular Apparatus................................................................... 45
3.1 Tubulovascular Proximities Outside
the JGA as Parts of the Tubulovascular
Complex of the Nephron....................................................................... 45
3.2 Glomerulus ............................................................................................... 47
3.2.1 Overview ............................................................................................... 47
3.2.2 Mesangial Cells in the Glomerular Stalk and
the Centrolobular Region of the Glomerulus ................................ 47
3.2.3 Peripolar Cells...................................................................................... 50
3.3 Morphological Basis of Fluid Balance in the Interstitium
of the Juxtaglomerular Apparatus........................................................ 52
3.4 Cortical Interstitium and Lymph Vessels............................................ 59
3.5 Innervation of the Juxtaglomerular Apparatus.................................. 61
VIII Table of Contents
Chapter4 lntrarenal Distribution of the Different Components
of the Renin-Angiotensin System .................................................................... 69
4.1 Renin.......................................................................................................... 69
4.1.1 Intrarenal Distribution of Renin....................................................... 69
4.1.2 Factors Influencing the Localization of Granulated Cells
in the Renal Arterial Tree................................................................... 80
4.1.3 Renin-Positive Cells of Different Origin?....................................... 84
4.1.4 Quantitative Evaluation of Histochemical and
Immunohistochemical Experiments in Relation
to the Renin Status of the Kidney .................................................... 87
4.2 Angiotensins ............................................................................................. 89
4.3 Angiotensin-Converting Enzyme.......................................................... 94
4.4 Angiotensinogen ...................................................................................... 97
4.5 Angiotensinases........................................................................................ 99
4.6 Nonrenin Angiotensin-Forming Enzymes .......................................... 100
ChapterS Synthesis and Traffic of Renin in Epithelioid Cells ...................................... 103
5.1 Granulopoiesis in Epithelioid Cells and Packaging
of the Secretory Product ......................................................................... 103
5.2 Renin Synthesis and Activation ............................................................ 109
5.3 Epithelioid Cell Secretory Granules Viewed as Lysosomes ............ 113
5.3.1 Lysosomal Enzymes as Constituents of Renin Granules ............. 113
5.3.2 Autophagic Phenomena in Renin Granules ................................... 117
5.3.3 Renin Granules and Lysosomotropic Substances ......................... 119
5.3.4 Exogenous Tracers and Renin Granules ......................................... 122
5.3.5 Conclusions and Outlook .................................................................. 125
ChapterS Morphology of Renin Release from Epithelioid Cells ................................. 127
Chapter7 Physiology, Pathophysiology, and Biochemistry of Renin Secretion ...... 137
7.1 Experimental Models .............................................................................. 137
7.1.1 Studies in the Intact Organism .......................................................... 137
7.1.2 The Kidney In Situ .............................................................................. 138
7.1.3 The Isolated Perfused Kidney ........................................................... 138
7.1.4 Kidney Slices ........................................................................................ 139
7.1.5 Isolated Glomeruli .............................................................................. 140
7.1.6 Isolated Cells ........................................................................................ 140
7.2 Renal Baroreceptor Mechanism ........................................................... 141
7.3 Tubular Signals, Renin Secretion, and Vascular Reactions -
The Macula Densa Hypothesis ............................................................. 144
7.3.1 Acute Tubulovascular Interactions ................................................... 145
7.3.2 Location of the Tubular Sensor. ........................................................ 147
7.3.3 The Macula Densa Signal.. ................................................................ 147
7.3.4 Concluding Remarks .......................................................................... 150
7.4 Renal Nerves and Renin Secretion ....................................................... 151
Table of Contents IX
7.5 Hormonal Signals Influencing Renin Secretion ................................ 154
7.5.1 Dopamine ............................................................................................. 154
7.5.2 Prostaglandins and Related Products .............................................. 155
7.5.3 Kallikrein and Kinins ......................................................................... 157
7.5.4 Histamine .............................................................................................. 159
7.5.5 Platelet-Activating Factor .................................................................. 160
7.5.6 Vasoactive Intestinal Polypeptide ..................................................... 160
7.5.7 Acetylcholine ........................................................................................ 161
7.5.8 Atrial Natriuretic Factor .................................................................... 162
7.5.9 Angiotensin ........................................................................................... 166
7.5.10 Antidiuretic Hormone ........................................................................ 169
7.5.11 Neuropeptide Y ................................................................................... 170
7.5.12 Other Hormonal Agents ..................................................................... 171
7.5.13 Synopsis of Hormonal Signals .......................................................... 172
7.6 Intracellular Control of Renin Release................................................ 173
7 .6.1 Introductory Remarks ........................................................................ 173
7.6.2 Role of Adenosine 3',5'-Cyclic Monophosphate ........................... 173
7.6.3 Role of Guanosine 3',5'-Cyclic Monophosphate .......................... 175
7. 6.4 Role of Calcium ................................................................................... 176
7.6.5 Role of Calmodulin ............................................................................ 180
7.6.6 Role of Diacylglycerol and Protein Kinase C ................................ 180
7.6.7 Interaction of Messengers .................................................................. 181
7.6.8 A Possible Explanation of the "Calcium Paradox"
of Renin Secretion ............................................................................... 182
7.6.9 Summary and Conclusions ................................................................ 184
7.7 Secretion of Prorenin .............................................................................. 185
7.8 Renin Synthesis and Secretion .............................................................. 189
Chapter 8 Electrophysiology of Epithelioid Cells ........................................................... 195
Chapter 9 lntrarenal Renin-Angiotensin System ............................................................. 197
9.1 Local Renin-Angiotensin Systems ........................................................ 197
9.2 Intrarenal Formation of Angiotensin II .............................................. 198
9 .2.1 Systemic Origin of Angiotensin I and II......................................... 199
9.2.2 Components of the Renin-Angiotensin System
in the Renal Interstitium and Renal Lymph................................... 200
9.2.3 Alternative Pathways of Angiotensin Formation .......................... 203
9.2.4 Intracellular Generation of Angiotensin II ..................................... 203
9.3 Renal Effects of Angiotensin II ............................................................ 204
9.3.1 Effects on Renal Hemodynamics ..................................................... 204
9.3.2 Angiotensin II and the Glomerulus ................................................. 207
9.3.3 Control of Sodium Excretion by Angiotensin II ........................... 209
9.4 Renin-Angiotensin System in the Control of Renal
Hemodynamics ........................................................................................ 210
9.5 Summary and Conclusions .................................................................... 213
X Table of Contents
Chapter 10 Metaplastic Transformation Between Smooth Muscle Cells
and Epithelioid Cells ........................................................................................... 215
Chapter 11 Long-Term Modulation of Renin Synthesis and Secretion ........................ 221
11.1 Relationship Between Renal Renin Content
and Renin Secretion................................................................................ 222
11.2 Uniform Reaction to Different "Stimuli"
of Renin Synthesis?................................................................................. 224
Chapter 12 lnterspecies Variations of the Juxtaglomerular Apparatus
in Mammals ........................................................................................................... 225
12.1 Qualitative Differences ........................................................................... 225
12.2 Quantitative Differences ......................................................................... 226
Chapter 13 Phylogeny and Ontogeny of the Juxtaglomerular Apparatus ................... 231
13.1 Evolution of the Juxtaglomerular Apparatus
in Nonmammalian Vertebrates ............................................................. 231
13.2 Ontogeny of the Juxtaglomerular Apparatus in Mammals ............. 235
Chapter 14 Pathology of the Human Juxtaglomerular Apparatus ................................. 241
R. WALDHERR
14.1 Stimulation of the Juxtaglomerular Apparatus .................................. 241
14.1.1 Ischemic Kidney .................................................................................. 241
14.1.2 Reflux Nephropathy ........................................................................... 243
14.1.3 Glomerular Disorders ......................................................................... 243
14.1.4 Hartter's Syndrome and Related Disorders .................................... 245
14.1.5 Renin-Secreting Tumors ..................................................................... 250
14.2 Inhibition of the Juxtaglomerular Apparatus ..................................... 253
14.2.1 Primary Hyperaldosteronism ............................................................ 253
14.2.2 Miscellaneous Conditions ................................................................. 253
14.3 Conclusions .............................................................................................. 254
References ....................................................................................................................................... 255
Subject Index................................................................................................................................... 305