Clinical significance of determining nitric oxide synthesis regulators in chronic obstructive pulmonary disease in comorbidity with arterial hypertension

Dysregulation of the endogenous vasodilator nitric oxide (NO) is one of the possible common components of pathogenesis of chronic obstructive pulmonary disease (COPD) and hypertension (HTN). That makes it urgent to search for possible biomarkers reflecting these correlations.

The aim: to study the clinical significance of determination of L-arginine, arginase-1 and asymmetric dimethylarginine (ADMA) in blood plasma of COPD patients in conditions of cardiovascular comorbidity.

Material and methods. 133 individuals aged 40 to 64 years (mean age 56 [52; 60] years) were involved in the study. All the participants were divided into 2 groups: the main group included 109 patients with COPD, control group included 24 practically healthy persons. The groups were comparable by gender (p = 0.341) and age (p = 0.055), as well as by smoking status: all subjects had a history of tobacco smoking and were active smokers. Determination of L-arginine, arginase-1 and ADMA levels in blood plasma was made by means of enzyme immunoassay methodic using Cloud-Clone Corp. laboratory kits (China).

Results. Presence of COPD has a significant effect on the level of arginase-1: corresponding indexes were 1.40 [0.90; 5.90] ng/ml in the main group versus 1.07 [0.57; 1.75] ng/ml in control one (p = 0.013). There was also a tendency towards the influence of the disease on ADMA content, which was significantly lower in the group of patients with COPD: 98.8 [21.1; 114.5] versus 104.3 [96.3; 109.7] ng/ ml in the control group (p = 0.053). ADMA level in COPD patients with mild (79.05 [42.60; 129.15]), moderate (101.15 [92.08; 108.78]) and severe (109,80 [87,40; 179,80]) severity of bronchial obstruction was significantly higher than in patients with extremely severe (10.70 [10.40; 11.18]) burden of the disease (p = 0.007). Concentration of arginase-1 was higher in the group of COPD with concomitant arterial hypertension: 2.11 [0.99; 8.9] versus 1.10 [0.90; 1.2] ng/ml in the COPD group without hypertension and 1.07 [0.57; 1.75] ng/ml in control group (p < 0.01). The level of L-arginine was statistically significantly lower in the COPD group with concomitant arterial hypertension comparatively to COPD group without hypertension and the control group: 9.6 [7.10; 12.30] versus 11.2 [9.28; 15.03] µg/ml and 10.95 [9.97; 11.83] µg/ml, respectively (p = 0.029).

Conclusion. The levels of arginase-1 and ADMA are associated with the presence of COPD in a patient. The levels of ADMA, L-arginine, arginase-1 and the ADMA/L-arginine ratio observed in the blood are associated with the characteristics of the clinical course of COPD. The presence of COPD and hypertension comorbidity in a patient also significantly affects the content of arginase-1 and L-arginine.