A considerable amount of information has been accumulated concerning the effect of various hypotensive agents on the pulmonary circulation. A detailed account on these observations was given recently by one of us (Halmagyi, 1957). Most of these studies were carried out in patients suffering from mitral stenosis. It was concluded that the increase of pulmonary vascular resistance in this disease is due both to organic changes and to vasoconstriction, the latter being mediated by the nervous system (Halmagyi et al., 1953). No uniform action was, however, obtained by drugs acting on different parts of the nervous system: even similar-acting drugs had a different effect on the pulmonary circulation. Tetra-ethylammonium (Halmagyi et al., 1953;Scott et al., 1955), dibenamine, sodium nitrite, and sleep (Halmagyi et al., 1953) resulted in a decrease in pulmonary arterial pressure and resistance. On the other hand, hexamethonium failed to influence pulmonary vascular resistance in carefully controlled observations carried out in patients suffering from mitral stenosis (Storstein and Tveten, 1954).There were many disadvantages in the therapeutic use of the substances mentioned above. The necessity of a parenteral rout of administration, their rapid excretion and, last but not least, their strong hypotensive action on the systemic circulation discouraged their widespread use. Schumann (1954, 1955) has recently pointed out that long-term peroral administration of serpasil to patients suffering from mitral stenosis resulted in an apparent amelioration of their complaints. This effect was attributed by him to general sedation and bradycardia, brought about by this medicament. It was therefore decided to investigate the effect of serpasil on the lesser circulation.
Elevation of pressure in the pulmonary veins, with a consequent elevation of pressure in the pulmonary capillaries and pulmonary artery has for many years been invoked to explain pulmonary hypertension in both mitral stenosis and left ventricular failure. Ignoring the possibility of pulmonary vasoconstriction, this hypothesis was in complete accordance with the " mechanistic " concept of the regulation of pulmonary pressure, emphasized recently by Cournand (1947Cournand ( , 1950 and Hamilton (1951). It was based mainly on the relative refractoriness of the pulmonary circulation towards substances affecting the systemic circulation.It was soon established, however, that elevation of the pulmonary venous pressure is only partly responsible for the high pressure in the pulmonary artery that is observed in heart failure. Elevation of pulmonary " capillary " pressure beyond the colloid osmotic pressure of plasma causes an increase in the pulmonary pressure gradient (Dexter et al., 1950), as a result of an increase of the pulmonary arteriolar resistance. Lewis et al. (1952), emphasize that in mitral stenosis this increased arteriolar resistance is a physiological counterpart to the anatomical changes observed in the small pulmonary arteries by Parker and Weiss (1936) and Larrabee et al. (1949). In face of this " static " theory of increased pulmonary arteriolar resistance it seems hard to understand why the presence or absence of heart failure raises or lowers the pressure in the pulmonary artery, presumably without a change in the size of the stenosed orifice (Bloomfield et al., 1949;Bayliss et al., 1951), or in the lumen of the " statically" narrowed pulmonary arterioles. Not even an increase of the circulating blood volume explains this apparent contradiction. Nor does the decrease of pulmonary arteriolar resistance following mitral commissurotomy (Draper et al., 1951; favour this theory. On the other hand, no corresponding narrowing of the pulmonary vessels can be demonstrated in hypertensive heart failure despite a similar elevation of pulmonary arteriolar resistance (Borden et al., 1950). These data seem sufficient to support the view that anatomical factors alone cannot account for all the increase in pulmonary arterial pressure. The mechanism of this reversible elevation of pulmonary vascular resistance, therefore, needs further study.Anoxia, by producing widespread vasoconstriction in all parts of the circulation, elevates also pulmonary vascular resistance (Motley et al., 1947; LiUjestrand, 1948 ;Dirken and Heemstra, 1948; Doyle et al., 1951, etc.). Pulmonary hypertension following the administration of histamine was also observed in dogs by Dixon and Hoyle (1930). The vasomotor response to both these stimuli is a consequence of their direct chemical action on the pulmonary vessels. The significance of the nervous system as a source of vasomotor stimuli affecting the pulmonary circuit is generally underestimated. Kuntz (1946)
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