ABSTRACT
Pulmonary hypertension and pulmonary vascular diseases have been reviewed for this Lung Biology in Health and Diseases series three times previously, in volumes 14, 28, and 99. The pathogenesis of pulmonary arterial hypertension (PAH) had been dissected each time, and it is tempting to look back and identify the key words and concepts that were emblematic of the state of knowledge at the time of writing these books in 1979, 1989, and 1997. To begin with volume 14, the term “primary” pulmonary hypertension was then used and also in the 1975 WHO definition of “unexplained pulmonary vascular disease.” Wrestling with a large number of published reports, many anecdotal, the authors concluded: “In the naturally occurring disease not attributed to aminorex, primary pulmonary hypertension is by and large a disease of young women.” Familial clusters of primary pulmonary hypertension were known at this time, but of course not the name of the gene. Factors associated with female maturation were considered as pathogenetically important, but “no specific hormone or endocrine factor had been identified in these patients.” Autoimmune mechanisms were discussed and the authors concluded that “at least some occurrences of primary pulmonary hypertension show a common etiology with autoimmune disease processes.” The first epidemic of diet druginduced primary pulmonary hypertension was fresh in everyone’s memory, yet the authors had to admit that “all the experimental work to demonstrate the effect of chronic (drug) application on pulmonary hemodynamics and morphology has failed to produce significant alterations.” Wagenvoort favored vasoconstriction as important in the pathogenesis of primary pulmonary hypertension and a diagram illustrated the prevailing pathogenetic concept that connected “the dots” in the following fashion:
Individual pulmonary vascular hyperreactivity (genetic disposition) ? vasoconstriction? elevation of the pulmonary artery pressure? right ventricular hypertrophy.
