The Renal Papilla and Hypertension

286 Pages·1980·4.87 MB·English

by  Anil K. Mandal

The Renal Papilla
and Hypertension
The Renal Papilla
and Hypertension
Edited by
Anil K. MandaI, M.D., F.A.C.P.
Veterans Administration Medical Center and
University of Oklahoma College of Medicine
Oklahoma City, Oklahoma
and
Sven-Olof Bohman, M.D.
Karolinska Institute
Stockholm, Sweden
PLENUM MEDICAL BOOK COMPANY
New York and London
Library of Congress Cataloging in Publication Data
Main entry under title:
The Renal papilla and hypertension.
Includes bibliographical references and index.
1. Renal hypertension. 2. Renal papilla. I. MandaI, Anil K. II. Bohman, Sven
Olof. [DNLM: 1. Hypertension. 2. Kidney medulla. WG340 R393]
RC918.R38R46 616.6'1 80-15989
ISBN 978-1-4684-8117-4 ISBN 978-1-4684-811 5-0 (eBook)
DOl 10.1007/978-1-4684-8115-0
© 1980 Plenum Publishing Corporation
Softcover reprint of the hardcover 1s t edition 1980
227 West 17th Street, New York, N.Y. 10011
Plenum Medical Book Company is an imprint of Plenum Pu blishing Corporation
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
This book is dedicated to our beloved wives and children for their gracious
cooperation, which encouraged us in our venture.
This book was facilitated in large part through the support of the
Medical Research Service of the Veterans Administration, Washington, D. C.,
and by the Medical Service, Veterans Administration Medical Center, and the
Department of Medicine, University of Oklahoma at Oklahoma City, Oklahoma.
Contributors
SVEN-OLOF BOHMAN • Department of Pathology, Karolinska Institute,
Huddinge Hospital, S-141 86 Huddinge, Sweden
INGE NORBY BOJESEN • Institute of Experimental Hormone Research,
University of Copenhagen, DK-2100 Copenhagen, Denmark
MUKUL C. GANGULI • Hypertension Section, Department of Internal
Medicine, University of Minnesota Hospital and School of Medicine,
Minneapolis, Minnesota 55455
CATHERINE LIMAS • Department of Pathology, Veterans Administration
Hospital, and Departments of Laboratory Medicine and Pathology,
University of Minnesota School of Medicine, Minneapolis, Minnesota
55455
ANIL K. MANDAL • Department of Medicine, Veterans Administration
Medical Center and University of Oklahoma College of Medicine,
Oklahoma City, Oklahoma 73104
BASAB K. MOOKERJEE • State University of New York at Buffalo,
Buffalo, New York 14215, and Medical Research Service, Veterans
Administration Medical Center, Buffalo, New York 14218
ROBERT C. MUEHRCKE • Department of Medicine, West Suburban Hos
pital, Oak Park, Illinois 60302
E. E. MUIRHEAD • University of Tennessee Center for the Health
Sciences and Baptist Memorial Hospital, Memphis, Tennessee 38146
JOHN A. NORDQUIST • Renal Electron Microscopy Laboratory,
Veterans Administration Medical Center, Oklahoma City, Oklahoma
73104
ix
x CONTRIBUTORS
RAM V. PATAK • University of Kansas Medical Center, Kansas City,
Kansas 66103, and Medical Research Service, Veterans Administration
Medical Center, Kansas City, Missouri 64128
J. A. PITCOCK • University of Tennessee Center for the Health Sciences
and Baptist Memorial Hospital, Memphis, Tennessee 38146
WOLFGANG SIESS • Department of Internal Medicine, University Hos
pital, 0-8000 Munich 2, West Germany
DINKO susie • Institute for Medical Research, 1101 Belgrade,
Yugoslavia
LOUIS TOBIAN • Hypertension Division, University of Minnesota
College of Medicine, Minneapolis, Minnesota 55455
PETER C. WEBER • Department of Internal Medicine, University Hos
pital, 0-8000 Munich 2, West Germany
RANDALL MARK ZUSMAN • Harvard Medical School, Boston, Massa
chusetts 02115, and Cardiac and Hypertension Units, Medical
Services, Massachusetts General Hospital, Boston, Massachusetts
02114
Foreword
LOUIS TOBIAN
There are many reasons for suspecting that the medulla of the kidney is
involved in the pathogenesis of hypertension. Although our present
knowledge does not permit the assignment of a precise and exact role for
the medulla, there are so many indications of its involvement that this is an
appropriate time for the subject to be thoroughly reviewed, as Drs. MandaI
and Bohman have done in this volume.
The involvement of the renal medulla in hypertension was first strongly
indicated by the studies of Eric Muirhead. Studying renoprival hyperten
sion, he demonstrated that the injection of extracts of renal medulla could
prevent this type of hypertension in the dog, rabbit, and rat. Subsequently, a
number of experiments showed that implants of renal medulla could not
only prevent renoprival hypertension but also greatly reduce the level of
blood pressure in Goldblatt hypertension in the rat and rabbit. It was later
noted that the majority of the surviving cells in these medullary implants
were interstitial cells. Pitcock and Muirhead were able to culture these
interstitial cells, and implants of the cultured cells lowered blood pressure in
renoprival hypertension and Goldblatt hypertension, particularly in the rat.
We were able to confirm these general observations by employing implants
of medulla in "postsalt" hypertension. The medullary implants did indeed
bring the blood pressure down. The belief that the implants themselves were
the effective agent was strengthened even further by the finding that when
they were removed, their antihypertensive effect would disappear and the
blood pressure would rise again.
The interstitial cells secrete some interesting substances with vasoactive
properties. They have definitely been shown to secrete prostaglandins E2
and F2", which of course are very powerful vasoactive agents, and they also
LOUIS TOBIAN • Hypertension Division, University of Minnesota College of Medicine,
Minneapolis, Minnesota 55455.
xi
xii LOUIS TOBIAN
secrete a neutral lipid material with strong antihypertensive properties.
Moreover, another cell in the renal medulla-the collecting duct cell-also
has a rich supply of the enzyme that can convert arachidonic acid into
prostaglandins. There are thus two types of cells in the renal medulla that
are able to synthesize prostaglandins, making the renal medUlla one of the
tissues in the body with the richest supply of prostaglandin cyclooxygenase,
equaled only by the seminal vesicles themselves. One can therefore look
upon the renal medulla as potentially a very active prostaglandin factory.
The renal medulla also contains the collecting ducts, which, as the last bit of
renal tubule that the urine passes through before emerging into the renal
pelvis, have "the last word" with regard to the ultimate excretion of sodium
in the urine. Since sodium handling is so intimately involved with the
process of hypertension, this particular medullary structure could be of
pivotal importance in the hypertensive process from the sodium standpoint
alone. Of course, the ascending limb of the loop of Henle also has an
extremely active sodium transport system, and this provides the driving
force for the countercurrent multiplier system that produces a concentration
gradient for NaCI and urea from the tip of the papilla toward the cortex.
The very high concentration of N aCI and urea in the papilla is a key ele
ment in the conservation of body water.
It is now quite definitely known that the prostaglandins have a pro
found influence on the concentration of NaCl in the papilla of the kidney.
The administration of prostaglandin synthesis inhibitors, such as indo
methacin or meclofenamate, can cause a doubling of the sodium concentra
tion in the renal papilla. It is thought that this is primarily the result of
enhancement of sodium transport out of the ascending limb and the collect
ing tubules or ducts after a profound inhibition of prostaglandin synthesis.
These are two more examples in which the level of prostaglandin E2 in the
papilla and the level of sodium in the papilla appear to go in opposite direc
tions. This may turn out to be a common physiological relationship and
indicates that prostaglandin levels have a very profound governing influence
on the concentration of N aCI in the papilla.
One might question what the concentrations of N a and Cl in the
papilla have to do with hypertension. Hrst of all, such concentrations would
influence the conservation of water in the body. Furthermore, we have
observed repeatedly that all forms of experimental hypertension appear to
be characterized by an abnormally low concentration of sodium in the
papilla. The precise reason for the relationship between the sodium
concentration in the renal papilla and the presence of hypertension has not
been clearly elucidated, but the low sodium concentration in this region
appears to be a part of the general hypertensive process. An alteration in
prostaglandin content may be related to this lowering of papillary sodium
concentration. Moreover, in earlier studies, it was noted that the number of
FOREWORD xiii
lipid granules in the cytoplasm of the interstitial cells was also greatly
reduced, and that this reduction correlated very strongly with the reduction
of sodium concentration in the renal papilla. This general picture of low
lipid granules in the interstitial cells and low sodium concentration in the
papilla was observed in four distinct forms of experimental hypertension.
It has also been pointed out by Moffat that the descending vasa recta
are invested with smooth muscle cells and could therefore undergo vaso
constriction or vasodilation. Originally, in an effort to study the process of
autoregulation in a papilla from a hypertensive rat, the plasma flow to the.
renal papilla was measured in various types of experimental rat hyperten
sion. It was found that all forms of experimental rat hypertension could be
characterized by reduced plasma flow to the renal papilla, even though the
flow to virtually every other organ was at normal levels, implying a dispro
portionate amount of vasoconstriction in the vessels supplying the papilla.
This would suggest that the circulation to the papilla was involved in the
hypertensive diathesis to a greater extent than was the circulation to all
other vascular beds. This conclusion is suggested by the fact that the
papillary vascular resistance increased enough to actually reduce blood
flow, whereas in all other vascular beds the resistance also increases, but not
sufficiently to actually bring blood flow to lower than normal levels.
One can thus find a myriad of abnormalities in the renal papilla in
various forms of experimental hypertension. These findings suggest a
definite involvement of the renal papilla in the hypertensive process and
imply that a number of papillary functions are distinctly abnormal during
hypertension.