We characterized the nasal contribution to exhaled nitric oxide (NO) at rest and during breathholding in humans. Exhaled NO was greater during nose breathing (141 +/- 17 nl/min/M2, mean +/- SEM) compared with mouth breathing (68 +/- 6 nl/min/M2, n = 8, p < 0.001). After voluntary closure of the soft palate (VCSP) to eliminate nasal NO, exhaled NO from the mouth decreased further (30 +/- 4 nl/min/M2, p < 0.001). Release of NO into nasal passages during VCSP (217 +/- 19 nl/min/M2) was greater than exhaled NO during nasal breathing (141 +/- 17 nl/min/m2, p < 0.001), suggesting that nasal NO is taken up by the respiratory tract. During mouth breathing or nose breathing, NO concentrations sampled with a bronchoscope were higher in the nasopharynx than at the epiglottis or in the trachea in five subjects. Increased peak exhaled NO after a breathhold (33 +/- 7 ppb) was reduced (10 +/- 4 ppb, p < 0.001) after balloon occlusion of the nasopharynx. NO concentration during breathholding increased to a greater extent in the nasopharynx than in the pharynx or trachea. We conclude that the majority of exhaled NO at rest and during a breathhold originates in the nasopharynx.

No abstract

To define the site of release and factors modulating exhaled nitric oxide (NO) during exercise in humans, we measured exhaled NO output during exercise, during exercise after balloon occlusion of the nasopharynx (to exclude nasal NO), and at rest with isocapneic hyperventilation or dobutamine infusion. Exhaled NO output increased from rest to exercise (57 +/- 10 to 171 +/- 30 nl.min-1.m-2; P < 0.003; n = 8). Exclusion of nasal NO reduced exhaled NO at rest and during exercise. Calculated nasal contribution at rest (53 +/- 5%) decreased during exercise (29 +/- 6%; P < 0.05), whereas nonnasal contribution increased (47 +/- 5 to 71 +/- 6%; P < 0.05). Isocapneic hyperventilation at rest increased exhaled NO output (51 +/- 8 to 94 +/- 22 nl.min-1.m-2; P = 0.05). Dobutamine infusion did not increase exhaled NO output. We conclude that nasal exhaled NO decreases (and nonnasal exhaled NO increases) with exercise. We also conclude that, under the conditions of this study, increased exhaled NO output during exercise is more closely related to increased ventilation than to increased blood flow.

No abstract

Experiments were carried out to test the hypothesis that intact endothelium is required for hypoxia-induced contractions of pulmonary vascular muscle in vitro. To study this possibility, we cut pairs of transverse strips from main pulmonary arteries of pigs, removed the endothelium from one strip, and mounted the strips on force transducers in separate tissue baths. After an adaptation period of 4-6 h at an oxygen tension of 40 torr, strips with intact endothelium contracted spontaneously when the oxygen tension was decreased from 140 torr to near zero torr (6.5 +/- 1.1 gm-wt/cm2, mean +/- SEM) whereas strips without endothelium contracted significantly less (1.0 +/- 0.3 gm-wt/cm2, p less than 0.001, n = 14 pairs). However, strips with and without endothelium contracted equally in response to incremental concentrations of norepinephrine. Each of several drugs (atropine, propranolol, phentolamine, or indomethacin, each 10(-5) M) had no effect on hypoxia-induced contractions when added to the bath prior to hypoxia. Similarly, a decrease in bath pH from 7.4 to 7.2 had no effect. Because we suspected that the endothelium might be releasing a mediator causing increased tone in response to hypoxia, we cleansed the bath during hypoxia, but this maneuver did not change hypoxia-induced contractions. Placing strips with intact endothelium close to strips without endothelium and measuring tension in the bath during hypoxia did not induce contractions in the strip without endothelium. We conclude that an intact endothelium is necessary for hypoxia-induced contractions in vitro in main pulmonary arteries from pigs. Although main pulmonary arteries are not primarily responsible for hypoxic vasoconstriction in vivo, our findings suggest a possible role for endothelium in the pulmonary vascular response to hypoxia.