[Vasodilators in acute pulmonary embolism: promising directions of fundamental research (literature review)].

Abstract

Background: Acute pulmonary embolism (PE) is the third leading cause of cardiovascular mortality after ischemic heart disease and stroke. Along with thrombolysis, reducing pulmonary vascular resistance in PE is one of the important pathogenetic ways of treating this pathology. The article presents a review of current literature data on the prospects for fundamental research into potential pulmonary vasodilators. A vasodilator used in clinical practice should be selective, if possible, for pulmonary vessels, not contribute to the aggravation of arterial hypotension, and not have a negative inotropic effect on the heart.

Objective: The purpose of this study was to analyze the available literature data on experimental research aimed at using vasodilators in modeling of PE in animals. The publications were retrieved from such databases as PubMed, Scopus, Web of Science, and Russian Science Citation Index.

Results and discussion: Since the development of pulmonary vasoconstriction in PE is promoted by neurogenic, humoral, and local mechanisms, it is impossible to single out the only key 'target' for the use of a vasodilator. Promising areas of research may include the search for new nitric oxide donors and the study of the vasodilator properties of such compounds as 1.2-propanediol and N-nitroso-N-morpholino-amino-acetonitrile. It is also necessary to study the vasodilator properties of argon as a potential agonist of GABA receptors in pulmonary vascular smooth muscle cells. Selective action on Ca2+, K+, and Na+ ion channels in pulmonary vascular smooth muscle cells could be a potential method of vasodilation in pulmonary thromboembolism. Piezo1 mechanosensitive channels of the pulmonary vascular endothelium may be a pharmacological target for vasodilation in PE. Further study of the mechanisms regulating intrapulmonary and bronchopulmonary shunt blood flow is also necessary to find new approaches to reducing pulmonary vascular resistance in PE. The effects of vasodilators in PE could be more pronounced if pathogenetic constrictor neurogenic mechanisms are eliminated simultaneously with their use. One of the approaches to reducing the neurogenic component of the constrictor reaction of pulmonary vessels in PE conditions could be the effect on inhibitory presynaptic receptors located at the endings of sympathetic nerves.