180 TIPS - April 1983

Books Hypertension review ? Frontiers in Hypertension Research o '~

edited by John H. Laragh, Fritz R. Biihler and Donald W. Sedin, Springer-Verlag, 1981. DM92, US $41.90 (xxxix + 628pages) 1SBN 0 387 90557 X

This book comprises the proceedings of an international symposium, initiated by Dr John Laragh and organized by him together with Dr Donald Seller and Dr Fritz Biihler and held over three days in New Orleans in May 1980. These three were also, appro- priately, the editors of the proceedings. The organizers intended to bring together scientists from all the varied disciplines per- tinent to hypertension research to focus them on controversial, or unresolved, issues of the mechanisms of pathogenesis (e.g. the role of sodium, sodium transport abnormalities and abnormalities in sym- pathetic nerve function and in the renin-angiotensin-aldosterone system). Naturally, as with any symposium organ- ized by these distinguished investigators, there was particular emphasis on the mean- ing and role of renin, volume-factors in hypertension and the emerging question of whether essential hypertension should be considered and treated as a single entity, or as a complex of entities in some of which the hypertension is maintained chiefly by excess angiotensin II or other vasocon- strictors, and in others of which the hyper- tension is chiefly maintained by excess volume.

The approach taken was to define 18 'frontier' topics, each of which was intro- duced by a longer position paper presented by a leader in research in that field and elaborated on by a series of shorter papers and a following discussion published in its entirety. The 18 topics included: role of dietary sodium; sodium transport (Na ÷ + K + membrane pump and volume over- load); role of prostaglandin-kinin interac- tions; whole body autoregulation and kid- ney function; a variety of topics related to volume v. vasoconstriction as factors; the role of the renal and extra-renal renin-angiotensin-aldosterone system and their control; the sympathetic nervous sys- tem; causes of vascular injury; modes of action of /3-blockers and of converting- enzyme inhibitors and angiotensin II antagonists.

Although considered in this symposium over 2 years ago, most of the frontier topics

are still important and the presentations are always pertinent and sometimes should be required reading for hypertension re- searchers. Naturally, some advances have occurred since the symposium and some topics need re-examination in the light of new information, e.g. the efficacy of diet- ary salt restriction, the role ofNa ÷ transport abnormalities and the role of angiotensin II. One topic has since emerged which was mostly neglected in that symposium, poss- ibly because it was then insufficiently developed, i.e. the importance of altered Ca ~+ handling as a generalized membrane defect in the pathogenesis of hypertension.

However, this volume provides a valu- able initiation to nearly all areas of current interest in hypertension research. The posi- tion papers provide an excellent, if suc- cinct, background which sets forth areas of agreement and disagreement. The brief papers are concise summaries of work by various groups, often presenting contrast- ing views, and the discussions are often lucid, providing a new insight into the areas being considered. The volume has been

carefully edited and this is most obvious in the quality and clarity of discussion mater- ial. There is an index which is adequate but fairly superficial, apparently prepared by the publisher.

In summary, this 628 page volume is valuable, if not essential, reading for those who are involved, or wish to be involved, in hypertension research. It will be 'particu- larly helpful to those who wish to broaden their understanding of the inter-relations between various research areas and obtain initial insight into evidence underlying many controversies and the thinking of proponents of various views. Its deficien- cies are few and are related to the particular areas of interest or disinterest of the organizers and the limitations in depth of analysis inherent in a symposium proceed- ing of this type.

E. E. DANIEL

The author is Professor in the Department of Neurosciences, McMaster University, Hamdton, Ontario, Canada.

Aspirin update Acetylsalicylic Acid - New uses for an old drug.

edited by H. J. M. Barnett, J. Hirsh and J. Fraser Mustard, Raven Press, 1982. $53.04 (x + 278 pages) ISBN 0 89004 647 6

Salicylic acid in the form of powdered wil- low bark has been used as an anti- inflammatory and antipyretic agent for cen- turies. At the beginning of this century, acetylsalicylic acid (aspirin) was recog- nised as being better tolerated than sodium salicylate and unravelling the mode of action of aspirin and identifying new therapeutic uses for this drug still preoc- cupies many medical scientists, as illus- trated by this book which contains the pro- ceedings of a conference held in Canada in April 1980.

The first few chapters review the phar- macokinetics and effects of aspirin on arachidonic acid metabolism, and the role of prostaglandins in infammafion, haemo- stasis and thrombosis. There is a very inter- esting review on the central and peripheral mechanisms involved in the analgesic activity of aspirin. The effect of aspirin on various organ and tissue functions is consi- dered with chapters on the drug's irritant

effect on the gastric mucosa, its effect on temperature regulation and on reproduc- tion, particularly primary dysmenorrhoea. The non-steroidal anti-inflammatory drugs are currently used to treat this disorder, the fenamates being more effective than aspirin or indometacin, possibly because the former inhibit some of the effects of prosta- glandins in addition to inhibiting their synthesis. The role of prostaglandins in maintaining the patency of the ductus arteriosus of the foetus is also discussed. When blood oxygen tension increases at birth, prostaglandin levels fall, contributing to closure of the ductus, but this is often delayed in premature babies and can be cor- rected by the use of non-steroidal anti- inflammatory drugs.

The basis for the use of aspirin as an anti- thrombotic agent is well reviewed by Kel- ton. Platelet derived thromboxane A~ induces platelet aggregation, but its action is opposed by prostaglandin h (prostacyc- lin) from the blood vessel walls. In-vitro experiments suggest that aspirin is equipo- tent in inhibiting both prostanoids, but since platelets lack nuclei, unlike endothelial cells, they cannot regenerate enzymes inac- ' tivated by aspirin and in-vivo evidence suggests that, forttmately, only very high doses of aspirin will inhibit prostacyclin formation and augment thrombosis.

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Five chapters deal with the clinical appli- cations of aspirin as an antithrombotic agent, with accounts of clinical trials in patients with cerebrovascular disease, coronary-artery disease and other thrombo- vascular disorders. Inevitably, there is a degree of overlap with these chapters, but one interesting finding to emerge is that males respond much more favourably than females to the antithrombotic effects of aspirin, not only in the clinical situation but in animal models as well. It is recognised that human males are at greater risk from thrombosis than are females, so the prophylactic use of aspirin goes some way to redress the balance.

Finally, consideration is given to the adverse effects of aspirin and the methodological problems of conducting long-term clinical trials. There are certainly several chapters in this book which will be compulsive reading for devotees of this fascinating drug.

It makes you feel good to be a man.

KEITH GREEN

The author is Scmor Lecturer in Pharmacology in the School o f Pharmacy, Portsmouth Polytechnic, Portsmouth, U.K.