PHARMACOLOGY AND CARDIOVASCULAR REFLEXES CARL F. SCHMIDT* The growth ofmodern pharmacology out ofancient, tradition-ridden Materia Medica into a respected member of the family of basic medical sciences is directly traceable to the conviction of Rudolf Buchheim that "Pharmakologie ist vielmehr eine theoretische d.h. erklärende Wissenschaft , und der Physiologie so nahe verwandt dass man sie mit vollem RechtealseinenTheilderPhysiologiebezeichnenkann" (i). ("Pharmacology is rather a theoretical science, and so closely related to physiology that it can rightly be considered a part ofphysiology.") Acting on this conviction , Buchheim set up a laboratory in his own home, and here he and his colleagues Friedrich Bidder and Carl Schmidt and his pupil and successor Oswald Schmiedeberg began the first systematic attempts at learning what drugs really do (2). Schmiedeberg subsequently went on to become director ofthe first University Department ofPharmacology in Strasbourg in 1872 and (with Naunynand Klebs) to establish the firstjournal devoted to pharmacology (3). Within the next half-century departments ofpharmacology were established in every major university in the world, and the first heads ofmost of these were trained under Schmiedeberg. His definition ofpharmacology is, therefore, a matter ofmore than passing interest: "Pharmakologie ist die Lehre von den im lebenden tierischen Organismus durch chemisch wirkende Substanzen, mit Ausnahme der assimilierbaren Nährstoffe, hervorgebrachten Veränderungen, die man im wahren Sinne des Wortes als physiologische Reaktionen bezeichnen kann" (4). ("Pharmacology is the study ofthe.changes brought about in living organisms through substances which act chemically [excluding foodstuffs]; these changes can be designated physiological reactions in the true sense ofthe word.") * Emeritus Professor of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia , Pennsylvania. 207 Buchheim apparently proceeded from the start on the basis that drugs cannot introduce any new, mysterious functions into the body but can only increase or decrease existing functions, and the same concept was transmitted by Schmiedeberg to the young men who passed through his hands on their way to become the leaders of pharmacology of the generation which isjust now passing from the scene. By 1920 the idea was quite generally accepted that the first step toward understanding the effects ofa drug is to understand the physiological (including biophysical and biochemical) background upon which it acts. From this viewpoint, any type ofexperimental study that will elucidate the latter comes within the scope ofpharmacology . Since a drug-induced change in the activity ofone part ofthe body is likely to lead to indirect effects on other parts, which may contribute to or even dominate the over-all result, pharmacology inevitably becomes interested in mechanisms through which indirect effects may be brought about. Among such mechanisms, cardiovascular reflexes are prominent, and studies ofthese have attracted the attention ofpharmacologists for many years. In at least three ofthese areas pharmacologists have made outstanding contributions: viz., the Bezold-Jarisch reflex, the reflexes ofthe carotid sinus and aortic arch regions, and the corresponding mechanisms in the pulmonary circulation. In each case there were special reasons for attracting and holding pharmacological interest, but these reasons were different enough tojustify some inquiry and speculation. I. The Bezold-Jarisch Reflex When Bezold and Hirt (5) first demonstrated that intravenous injections of alkaloids of veratrum can cause hypotension and bradycardia (even temporary asystole), which effects are completely abolished or prevented by section ofthe vagus nerves, cardiovascular reflexes were a great novelty. Pharmacology was not yet established as a distinct discipline, for this did not happen until Schmiedeberg went to Strasbourg five years later. Before he took this step, he spent a sabbatical year in Leipzig, where he supplemented his previous training (which was largely in the chemical approach to physiology) with experience in the newer physical methods under the recognized master, Carl Ludwig (3). Here he must have learned about the cardioinhibitory, cardioaccelerator, and depressor nerves, the last having recently beendiscoveredbyCyonandLudwig (6); butsince Schmiedeberg and his pupils subsequently ignored Bezold's findings, one must assume 208 Carl F. Schmidt · Pharmacology and Cardiovascular Reflexes Perspectives in Biology and Medicine · Winter 1962 either that he did not know ofthem or did not rate them as items ofsurpassing interest. It was not untilJarisch (7) restudied the Bezold reflex in !937~42 that anything further came ofit (8). Following Jarisch's work, other laboratories...