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Increased plasma and salivary nitrite and decreased bronchial contribution to exhaled NO in pulmonary arterial hypertension


Andrei Malinovschi, Department of Medical Sciences: Clinical Physiology, Uppsala University, Avd. för klinisk fysiologi, Akademiska sjukhuset, Ing 35, 1 tr., SE-751 85 Uppsala, Sweden. Tel.: +46 184714407; fax: +46 184714938; e-mail:


Eur J Clin Invest 2011; 41 (8): 889–897


Background  Conflicting results on exhaled NO in pulmonary hypertension (PH) exist. Therefore, we analysed exhaled NO, as well as systemic and local nitrite, a possible alternative source of NO, in PH with regard to PH aetiology.

Methods  Exhaled NO at multiple flow-rates, as well as plasma and salivary nitrite and nitrate, was measured in 22 patients with PH and 21 healthy controls. Alveolar NO (CalvNO) and bronchial flux (J’awNO) were calculated using the slope–intercept model. Patients with PH were subdivided into pulmonary arterial hypertension (PAH) and PH WHO Groups II–IV, according to the WHO clinical classification of PH.

Results  Exhaled NO was reduced at flow-rates in the range of 20−200 mL s−1 in patients with PAH (n = 13) vs. PH WHO Group II–IV (n = 9) (P < 0·05 all). Patients with PAH had higher CalvNO than healthy controls [2·61 (2·23, 3·36) vs. 1.97 ppb (1·22, 2·49), P = 0·03] and similar to PH WHO Group II–IV (P = 0·51). Patients with PAH had lower J’awNO than patients with PH WHO Group II–IV or healthy controls [430 (371, 702) vs. 807 (557, 993) or 731 pL s−1 (580, 818), P < 0·05 both]. Subjects with PAH were characterized by higher levels of salivary and plasma nitrite than healthy controls (P < 0·05 both).

Conclusions  Patients with PAH have lower bronchial NO flux compared to healthy controls and patients with PH WHO Group II–IV along with elevated salivary and plasma nitrite compared to controls. This implies reduced bronchial NO synthase-derived NO formation in PAH. Increased alveolar NO levels were found in subjects with PH compared to controls, especially in subjects with PAH. This may reflect NO diffusion disturbances in the alveoli.