BOOK REVIEWS

HYPOTENSIVE DRUGS. Edited by M. Harington, London, 1956, Pergamon Press Ltd., 221 pages. Price $8.00.

This volume contains the proceedings of a symposium on hypotensive drugs and the control of vascular tone in hypertension which was held in April, 1956, under the auspices of the Bio- logical Council’s Coordinating Committee for Symposia on Drug Action. Twenty-two speakers from the United Kingdom and from five foreign countries participated in the symposium, which was organized in four sessions dealing with the chemistry, pharmacology, and clinical applications of hypotensive drugs and with factors involved in the control of vascular tone in hypertension.

The first section of the book deals with the chemistry and structure-activity relationships of most of the common classes of hypotensive drugs, special emphasis being placed on the gang- lionic blocking agents. Considerable progress is being made in the understanding of the structural characteristics of secondary, tertiary, and quaternary bases which determine such important pharmacologic attributes as ease of absorption from the intestine and relative activity of blockade at sympathetic and parasympathetic ganglia.

Much of the discussion in the pharmacologic section concerns the mode of act@ of reserpine, especially the significance of the fact that it stimulates the release of 5-hydroxytryptamine from the intestine, from the blood platelets, and from the brain. There seems to have been general agreement that an increase in circulating 5-hydroxytryptamine may well be the cause of some of the side-effects of reserpine but is probably not responsible for the hypotensive effect. The exis- tence of true synergism between reserpine and other hypotensive agents was regarded as still unproved.

.4n interesting suggestion concerning the mechanism of development of tolerance to the hypo- tensive action of ganglionic blocking agents is made by Dr. Eleanor Zaimis. She reviews the re- sults of experiments which indicate that ganglionic blocking agents may also act peripherally to sensitize arteriolar smooth muscle to the vasoconstrictor effect of epinephrine and norepinephrine.

In the section on clinical applications of hypotensive drugs, Professor McMichael gives a guardedly optimistic review of the results achieved in a series of 62 cases of malignant hyperten- sion treated with subcutaneous hexamethonium or pentolinium during the preceding 5 years. Professor Smirk expresses a preference for oral therapy with pentolinium and reserpine. He ap-

pears to be enlarging his indications for this form of therapy to include not only patients with Keith-Wagener Grade 3 and 4 fundi, but also most patients with hypertensive symptoms and even some of the asymptomatic cases with only moderately increased blood pressure levels. Dr. George Perera enters a plea for the use of adequate data on untreated controls as a basis for eval- uation of the effects of drug therapy on patients who are not in the accelerated phase.

The fiual section deals with the control of vascular tone in hypertension. Professor Clifford Wilson presents the evidence which has led him to believe that there is a common physiologic mechanism underlying all forms of persistent hypertension, regardless of the nature of the initiat- ing factor in the early stage. This common factor is probably a change in the chemical environ- ment of arteriolar smooth muscle which leads to a change in its responsiveness. Dr. Bjijrn Folkow offers a mechanical explanation of the way in which hypertrophy of the smooth muscle layer of the arteriolar wall may be responsible for an increase in peripheral resistance, even in the absence of orgauic narrowing of the lumen by arteriolar scterosis.

The discussion of the mechanisms involved in experimental renal hypertension reflects the difficulties which have arisen in connection with some of the established concepts as a result of the discovery of renoprival hypertension. No completely satisfactory hypothesis has been put forward to provide a common mechanism for the hypertension produced by unilateral renal artery constriction and that caused by bilateral nephrectomy. The hypothesis which seemed to receive most support in this symposium was the suggestion that the fundamental role of the kidney may be to maintain normal blood pressure by regulating some extrarenal pressor mechanism, possibly one of adrenal cortical origin.

This is a book which should be in the library of everyone who is actively engaged in the study of pathogenetic mechanisms in hypertension. Its virtues lie not only in the thoughtful presenta- tions of various points of view by the principal speakers, but also in the verbatim reports of the excellent general discussion which took place at the end of each session.

I<. A. E.