Dilatation Reserve of Pulmonary Arteries at Stages of the Chronic Obstructive Pulmonary Disease Model

To assess the state of pulmonary vascular mediator systems during the stepwise formation of the chronic obstructive pulmonary disease (COPD) model.

The COPD model was induced in rats by nitrogen dioxide (NO₂) inhalation for 60 days. At different stages of COPD (15, 30, and 60 days), the effect of reagents-vasodilators (β-adrenoceptor agonist isoproterenol, nitric oxide donor nitrosorbide, acetylcholine, activator of C-fibers capsaicin, corticosteroid beclometasone) on the isolated pulmonary arteries (diameter <0.5 mm) was studied. Vascular reactivity was assessed by determining isometric contraction (tension in milligrams) of arterial rings by using an electromechanical transducer.

All vasodilators dose-dependently decreased the vascular tone of pulmonary arteries isolated from intact rats. After 15 days of NO2 exposure, dilatation effect of low doses of vasodilators did not differ from that of intact specimens. The functional state of the adrenergic system deteriorated faster than that of the nonadrenergic noncholinergic system as reflected by the weakening of the isoproterenol relaxation effect. On prolonged NO₂ exposure, pulmonary arteries responded to the impact of all vasodilators with smaller relaxation. Dose dependence of the dilatation reaction disappeared for isoproterenol, capsaicin, beclometasone, and was less expressed for nitrosorbide and acetylcholine after 60 days of exposure.

In the course of COPD model generation, the functioning of almost all neurotransmitter systems of pulmonary artery wall was negatively affected. This led to a decrease in the influence of vasodilators on pulmonary artery vascular tone and could facilitate the development of pulmonary hypertension, which is typical of COPD.