Mechanisms underlying vasomotor regulation of regional pulmonary blood flow in normal and disease states

Abstract

Recent observations have suggested a complex multistage mechanism underlying the regulation of regional pulmonary blood flow by local hypoxia and hypercapnic acidosis, as well as underlying the more generalized pulmonary hypertension of over-all alveolar hypoxia and/or hypercapnia occurring at high altitude and with respiratory disease. This mechanism has eluded precise description at present, but a consensus appears to have agreed on the following characteristics: (1) a humoral agent acts on the small pulmonary arteries, probably through the alpha adrenergic system which has been demonstrated in these vessels, (2) this agent is a strong pulmonary vasoconstrictor, (3) it is most likely stored (ready for release) in a conveniently located depot, such as the periarterial mast cell; it is less likely to be generated by increased enzymatic activity in the lung parenchyma; and it is least likely to be a circulating agent activated by plasma factors, but these latter two possibilities cannot be ruled out. Although the effects of this mechanism in aggravating pulmonary hypertension and cor pulmonale are well recognized, the humoral agents and their release and generation (or a similar process with different agents) may also be important in entities such as high altitude, and heroin-induced pulmonary edema and pulmonary embolism. Entities in which the pulmonary vasoconstrictor responses to hypoxia may be absent, i.e., hepatic cirrhosis and familial dysautonomia, are not only characterized by systemic hypoxemia, as would be expected, but may also help eventually to elucidate the further detailed mechanisms of these responses.