Table Of ContentESSENTIAL HYPERTENSION
AN INTERNATIONAL SYMPOSIUM
BERNE, JUNE 7th-10th, 1960
SPONSORED BY CIBA
CHAIRMAN
F. C.REUBI
BERNE
EDITED BY
KD.BOCK P. T. COTTIER
BASLE BERNE
WITH 81 FIGURES
SPRINGER-VERLAG
BERLIN· GOTTINGEN· HEIDELBERG
1960
This book has also been published in German under the title
,ESSENTIELLE HYPERTONIE'
Ein internationales Symposion
ISBl\ 978-3-642-49607-3 ISBK 978-3-642-49899-2 (eBook)
Dor 10.1007/978-3-642-49899-2
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© by Springer-Verlag OHG
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Softcover reprint of the hardcover 1st edition 1960
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Contents
Opening remarks (F. C. REUBI). . . . . . VII
The m08aic theory of hyperten8ion (1. H. PAGE) . 1
Inheritance of high blood pre88ure (G. W. PICKERING) 30
The nature of e88ential hyperten8ion (R. PLATT) . . . 39
Discussion: Brod, Govaerts, GroHman, Peart, Pickering, Platt, Reubi,
Sarre, Schroeder, Taquini, Wilson. . . . . . . . . . . . . . . . 45
P088ible role of salt intake in the development of essential hypertension
(L. K. DAHL). . . . . . . . . . . . . . . . . . . . . . . . . 53
Renal hemodynamics, water and electrolyte excretion in essential hyper
tension (P. T. COTTIER) . . . . . . . . . . . . . . . . . . . . 66
Discussion: Brod, Cottier, Dahl, Freis, Hilden, Hoobler, Hood, Mach,
Platt, Reubi, Schroeder, Taquini . . . . . . . . . . . . . 83
Adrenocortical function and renal pre8sor mechanisms in experimental
hypertension (F. GROSS) . . . . . . . . . . . . . . . . . . . . 92
Possible relationship between salt metabolism and the angiotensin sy8tem
(W. S. PEART) . . . . . . . . . . . . . . . . . . . . . . . . 112
Discussion: Bock, Brod, Cottier, GroHman, Gross, Peart, Pickering,
Reubi, Wilson . . . . . . . . . . . . . . . . . . . . 121
Adrenocortical function in essential hypertension (J. GENEST, W. No-
WACZYNSKI, E. Korw, T. SANDOR, and P. BIRON) ......... 126
The 8ignificance of hyperald08teronuria in hyperten8ion (J. W ARTER,
J. SCHWARTZ, and R. BLOCH) . . . . . . . . . . . . . . . . . 147
Discussion: Brod, Dahl, Genest, Gross, MuHer, Peart, Reubi, Schroeder,
Schwartz, Wilson . . . . . . . . . . . . . . . . . 159
Therapeutic a8pect8 of 8alt re8triction (A. GROLLMAN) . . . . . . . . . 168
Mechani8m of hypotensive action of 8aluretic8 (E. D. FREIS) . . . . . 179
Discussion: Bock, Cottier, Ferrero, Freis, GroHman, Gross, Hoobler,
Hood, Plummer, Reubi, Sarre, Schettler, Schmid, Schroeder, Ta
quini, Wilson . . . . . . . . . . . . . . . . . . . . . . . . 192
The natural history of benign hypertension (P. BECHGAARD). . . . . . 198
The natural cour8e of malignant hyperten8ion (P. MILLIEZ, P. TCHERDA
KOFF, P. SAMA~Q, and L. P. REY). . . . . . . . . . . . . . . . 214
Discussion: Bechgaard, Brod, Govaerts, Hamburger, Hilden, Milliez,
Page, Pickering, Platt, Reubi, Sarre, Schroeder, Wilson . 231
Pharmacology of new hypoten8ive drug8 (A. J. PLUMMER). . . . . . . 240
Bretylium and guanethidine (clinical re8ult8) (T. HILDEN) 261
Combined dT1~g therapy of hyperten8ion (S. W. HOOBLER and P. LAUWERS) 270
IV Contents
Effects ot the administration ot saluretic drugs in the treatment ot arterial
hypertension (C. BARTORELLI) . . . . . . . . . . . . . . . . . 283
Discussion: Bartorelli, Brod, Freis, Genest, Gross, Hilden, Hoobler, Hood,
Page, Peart, Reubi, Schroeder, Wilson . . . . . . . . . . . . . 296
Survival rates in severe hypertension intensively treated with hydral'lzine
and ganglionic blockade (H. A. SCHROEDER and H. M. PERRY, jr.) . 307
The late eftects ot hypotensive drug therapy on renal tunctions ot patients
with essential hypertension (F. C. REUBI) . . . . . . . . . . . . 317
Late results of surgical therapy (sympathectomy and adrenalectomy)
(H. SARRE) . . . . . . . . . . . . . . . . . . . . . . . . . 332
Discussion: Arnold, Dahl, Ferrero, Freis, Hilden, Hoobler, Hood, Imhof,
Milliez, Peart, Pickering, Platt, Reubi, Sarre, Schroeder, Schwartz. . 347
Hypertension and its associated vascular diseases (P. IMHOF, 1. H. PAGE,
and H. DUSTAN) . . . . . . . . . . . . . . . . . . . . . . . 354
Preuntion and treatment ot "atheromatous complications" ot hypertension
(G. SCHETTLER) . . . . . . . . . . . . . . . . . . . . 360
Discussion: Cottet, Hoobler, Hood, Imhof, Schettler, Steinmann 380
Closing remarks (F. C. REUBI) . 383
List of authors 387
Subject index . 388
Participants in the Symposium
"ESSENTIAL HYPERTENSION"
Berne, 7th-10th June, 1960
Arnold, O. H., Medizinische Klinik der Stadtischen Krankenanstalten, Essen
(Germany)
Bartorelli, C., Universita di Siena, Istituto di Patologia Speciale Medica
e Metodologia Clinica, Siena (Italy)
Bechgaard, P., Medicinsk afdeling, Aarhus Universitet, Aarhus (Denmark)
Bock, K. D., OlBA Aktiengesellschaft, Basel (Switzerland)
Brod, J., Ustav pro Choroby Obilhu Krevniho, Praha-Krc (Czechoslovakia)
Cottet, J., Medecin consultant, Paris and Evian (France)
Cottier, P. T., Medizinische Universitats-Poliklinik, Bern (Switzerland)
Dahl, L. K., Brookhaven National Laboratory, Associated Universities,
Upton, N. Y. (USA)
Ferrero, C., Centre de Cardiologie, Hopital Cantonal, Geneve (Switzerland)
Freis, E. D., Veterans Administration Hospital, Washington, D. C. (USA)
Frey, 'V., Oberhofen am Thunersee (Switzerland)
Genest, J., Departement de recherches cliniques, Hotel-Dieu de Montreal,
Montreal (Canada)
Govaerts, P., Fondation Medicale Reine Elisabeth, Bruxelles (Belgium)
Grollman, A., University of Texas, Dallas (USA)
Gross, F., OlBA Aktiengesellschaft, Basel (Switzerland)
Hadorn, W., Medizinische Klinik der Universitat, Bern (Switzerland)
Hamburger, J., Hopital Necker, Paris (France)
Hilden, T., Diakonissestiftelsen, Kobenhavn (Denmark)
Hoobler, S. W., University of Michigan, Ann Arbor (USA)
Hood, B., Goteborgs Universitet, Medicinska Kliniken I, Goteborg (Sweden)
Imhof, P., Lory Spital, Bern (Switzerland)
Mach, R. S., Hopital Cantonal, Clinique Universitaire de TMrapeutique,
Geneve (Switzerland)
Milliez, P., Faculte de Medecine, Paris (France)
Muller, A. F., Hopital Cantonal, Clinique Universitaire de TMrapeutique,
Geneve (Switzerland)
Page, 1. H., Cleveland Clinic Foundation, Cleveland, Ohio (USA)
Peart, W. S., St. Mary's Hospital, London (Great Britain)
Pickering, Sir George, University of Oxford, Oxford (Great Britain)
Platt, Sir Robert, The Royal Infirmary, Manchester (Great Britain)
Plummer, A. J., OlBA Pharmaceutical Products Inc., Summit, N. J. (USA)
VI Participants in the Symposium "ESSENTIAL HYPERTENSION"
Reubi, F. C., Medizinische Universitats-Poliklinik, Bern (Switzerland)
Sarre, H., Medizinische Universitats-Poliklinik, Freiburg i. Br. (Germany)
Schettler, G., Krankenhaus Bad Cannstatt, Innere Klinik, Stuttgart
(Germany)
Schmid, A., Bern (Switzerland)
Schroeder, H. A., West Brattleboro, Vermont (USA)
Schwartz, J., FaculM de Medecine, Strasbourg (France)
Steinmann, B., Lory Spital, Bern (Switzerland)
Taquini, A. C., Universidad de Buenos Aires, Buenos Aires (Argentine)
Wilson, C., The London Hospital, London (Great Britain)
Opening remarks
By
F. C. REUBI
It is a great honour for me to open this symposium, and I
should like to extend to you a most cordial welcome and to thank
you for accepting our invitation. I am sure you will all wish me on
your behalf to express our sincere gratitude to elBA, Basle, for
financing this undertaking.
Although the question of arterial hypertension has commanded
the attention of research workers ever since its existence was first
discovered, we still seem to be a very long way from having solved
the problem. On the other hand, while it was once true to say that
medical research was confined to only a few countries, we can
derive satisfaction from the knowledge that today a great deal of
work has been accomplished during the past few years in both the
old and the new world, in the East and in the West. For this very
reason, it is becoming more and more important to ensure that
results should be compared, opinions exchanged, and trends of
research defined periodically on an international plane. The more
widely differing the concepts presented, the more fruitful we can
expect the resultant clash of ideas to prove. As men of science we
have no need to concern ourselves with the battles being waged in
the field of international politics. Let us therefore ignore such matters
and seek to reconcile our views here in a spirit of understanding and
open-mindedness. Let us banish all preconceived notions and
beware of allowing ourselves to be blinded by questions of dogma,
prestige, and personal pride.
Attending this symposium are some forty specialists from 12
different countries. The number of participants has deliberately
been limited and the discussions will be held in private. You will
all know yourselves from experience that an atmosphere conducive
to a frank exchange of views - views that are sometimes diametri
cally opposed - can only be established if the speakers cut
themselves off from the outside world. We have, however, made
allowance on the programme for two sessions in public. In today's
public session, we shall hear three lectures in which the problem of
the pathogenesis of hypertension will be dealt with from the general
VIII F. C. REUBI: Opening remarks
aspect. The second public session - to be held at the end of the
week in connection with the Annual Meeting of the Swiss Society
for Internal Medicine - will take the form of a panel discussion on
the treatment of hypertension. The symposium itself will be
entirely devoted to the study of two specific questions, the first
being the problem of the possible relationships between so-called
essential hypertension and salt and water metabolism, and the
second the long-term effects of anti-hypertensive therapy as regards
the clinical course of hypertensive disease. We are convinced
that, rather than attempt to cover the whole subject of essential
hypertension, it is a sound procedure to concentrate our attention
on certain particular aspects of this vast problem. Perhaps this
approach will enable us to get closer to our objective and finally to
reach agreement on a certain number of points - in which case we
shall be in a better position to offer some practical recommendations
when we come to our second public session.
You may possibly wonder why we chose these two topics for
discussion in preference to others. As regards the connections
between hypertension and salt and water metabolism, we have the
impression that this problem has become of great current interest
since the sali-diuretics were introduced in the treatment of hyper
tension, and that the whole question deserves to be reconsidered in
the light of recent endocrinological findings. As for the long-term
effects of purely hypotensive therapy on the course of the disease,
the time that has elapsed since effective anti-hypertensive agents
were first introduced should now be sufficient to enable us to make
a preliminary assessment of the value of such treatment. Since this
is a matter of major practical importance, we should certainly not
wait too long before undertaking a critical analysis of the results
obtained to date.
Let us hope that this symposium will prove of great help in
enriching our knowledge.
The mosaic theory of hypertension
By
I. H.PAGE
It has been some years now since I proposed the mosaic theory
of hypertension and it is time, I think, to review where it stands today.
Has it proved useful and is it likely to continue to do so ?
The mosaic theory had its background in the fact that thirty
years ago thinking in the field of infectious disease mostly prevailed,
not only in its own field, but in others as well. The search was often
limited to the finding of a single causative agent. If the typhoid
bacillus was isolated and cultured, this was the cause of the disease
and its elimination was the treatment. So those of us who worked
in other fields tried to find the cause of hypertension and the cause
of atherosclerosis. As a result of repeated failures, as many theories
sprang up as there were investigators. The chief contender for the
cause of hypertension in those days was the kidney. Many felt that
after GOLDBLATT's work, the kidney was the true, and only, cause
of essential hypertension. The fate of this view is an interesting
story but it is diverting.
As time passed, it slowly became evident that the problems of
cardiovascular disease and cancer were not likely to yield to an
attack on one front. It seemed unlikely that all types of hyper
tension and arteriosclerosis would be explained by single mecha
nisms. And it seems to me that reflection on the nature of the
circulation gives a clue as to why this is so. Arterial blood pressure
is one of the components of the system used to perfuse tissues with
blood. The problem of getting the right amount of blood to the
right part of the body at the right time is an amazingly complicated
and difficult one. To know where blood is available and from where
it can safely be withdrawn is a major problem in itself. It is not
surprising, then, that the body has developed a highly complex
system for carrying out this task efficiently. We shall again put this
wonderful mechanism to the test when gravitation has become but
a memory in our exploration of outer space. It is my guess that man
is more likely to have trouble with his cardiovascular responses to
weightlessness than with his control over his actions by his brain;
which is certainly a change.
Symposium Essential Hypertension I
2 1. H. PAGE:
I have suggested in the mosaic theory that the varied facets
which compose blood pressure control are in equilibrium with one
another and the final pressure level is determined by the equilibrium
point. Thus, if blood volume changes, neurogenic vasomotor tone
changes to keep the blood pressure at a constant level. While one
facet may temporarily playa dominant role in determining the
level, this does not mean that all the otherfacets cease functioning.
Just so in the hypertensive patient one facet may be dominant,
but the secondary facets are in equilibrium with it and, with the
passage of time, may themselves become primary.
Cllemicu/
Elusticity I<§=--+----'-'==----'--~~"-'-":.!.!....-_t------,[~ lIo/ume
Viscosity
Fig. 1. The mosaic theory of hypertension showing the equilibration of the various facets of
pressure control to provide for controlled tissue perfusion
This seems a simple concept indeed, with which no one should
quarrel, but few physicians truly understand it. For instance, it
explains why there are so many possible points at which the
mechanisms of blood pressure control can be blocked, for thera
peutic reasons. It explains why the clinical picture of hypertension
is so variable. Not the least of its virtues is that it makes thinking
about the disease orderly.
Beyond the physiological processes which I have included in the
octagon, I have further divided and grouped what seem to be
primary mechanisms of a variety of hypertensions. These groups
are: 1. nervous, 2. endocrine, 3. cardiovascular, and 4. renal. Again,
it must be recognized that while the nervous system may be predom-
