MODELING PULMONARY DIFFUSING CAPACITY AND RED CELL DISTRIBUTION

Hsia et al. (p. 1460) have developed a two-dimensional finite-element capillary model to study the effect of red cell distribution on CO uptake. Red blood cells are distributed uniformly, randomly, or in clusters within the capillary. At constant red cell density, the uniform distribution produces the largest CO diffusing capacity (DL_CO), whereas the clustered distribution produces the least. A random distribution of red blood cells within a single capillary segment reduces CO uptake by 30% and within several capillary segments by 50%. Thus redistribution of red blood cells within capillaries may account for 50% of the observed increase in DL_CO with exercise. The paper is discussed in an Invited Editorial by Forster (p. 1458).

	VASODILATORS AND ANGIOGENESIS

Exercise training induces angiogenesis in the exercised muscle. To examine the mechanism of this adaptation, Benoit et al. (p. 1513) studied the effects of nitric oxide, vasodilator prostaglandins, and adenosine on angiogenic growth factor gene expression in rats. Nitric oxide, given by intra-arterial infusion, was found to increase vascular endothelial growth factor mRNA in skeletal muscle. This and other results are consistent with the hypothesis that vasoactive substances released during exercise are responsible in part for the angiogenic response to exercise training.

	SYMPATHETIC ADAPTATIONS TO LEG TRAINING

Ray (p. 1583) determined the effect of 6 wk of one-legged cycling on the muscle sympathetic nerve activity (MSNA) response to 3 min of dynamic knee extension. Training increased peak oxygen uptake by 19% and lowered resting heart rate by 6 beats/min on average. Training failed to alter resting MSNA but did prolong the decrease in MSNA during dynamic knee extension. The prolongation of the decrease in MSNA during exercise was thought to be due to a training-induced attenuation of the muscle metaboreflex, which, in turn, prevented this reflex from overriding the sympathoinhibitory effect of the cardiopulmonary baroreflex.

	HE AND SF6 BOLUS WASHIN IN SHORT-TERM MICROGRAVITY

Dutrieue et al. (p. 1594) performed single-breath washout tests with He and sulfur hexafluoride (SF₆) in normal gravity and in short-term microgravity during parabolic flight. Bolus inspiration tests at different lung volumes produced results consistent with the phase III slope of conventional single-breath washout and showed little contribution to the slope by gas inspired in the mid-volume range. Gravity-dependent events at high and low volumes accounted for the differences in phase III slope between normal gravity and microgravity. Phase IV height was greater for SF₆ than for He. This suggests that residual volume airway closure or flow limitation occurred in close proximity to open airways, enabling diffusion to reduce concentration differences established by convective inhomogeneities during inspiration.

	WHY IS THE EFFECTIVENESS OF NASAL DILATOR STRIPS SO VARIABLE?

Adhesive nasal dilator strips are widely used in the belief that they relieve nasal congestion, reduce snoring, and enhance athletic performance. Dilator strips have been found to reduce nasal resistance to airflow substantially in some subjects but to have little or no effect on resistance in others. Amis et al. (p. 1638) examined the influence of dilator strips on external nasal geometry in normal subjects. Although the outward recoil force of the strips was consistent and essentially invariant over a wide range of flexion, the effect on the cross-sectional area of the nares varied nearly threefold among subjects, reflecting substantial intersubject variation in the compliance of the wall of the nasal vestibule. This variation in compliance may account for the wide range of responsiveness of nasal resistance to dilator strips in previous reports.

	ENDOTHELIAL MECHANISMS OF ARTERIOLAR DILATION

Endothelium-derived prostaglandins and nitric oxide have both been implicated in dilator responses of skeletal muscle arterioles. The roles of these factors in flow- and hypoxia-induced vasorelaxation were examined in arterioles from rat diaphragm by Ward et al. (p. 1644). The importance of nitric oxide was assessed by inhibition of nitric oxide synthase with arginine analogs, and that of prostaglandins was evaluated by inhibition of their production with indomethacin. Acetylcholine-induced arteriolar dilation was dependent on nitric oxide synthase and not altered by indomethacin treatment. In contrast, flow-induced dilation was blunted by arginine analogs or indomethacin and abolished by both in combination. Hypoxia-induced dilation was eliminated by indomethocin but not affected by arginine analogs. The results indicate that acetylcholine-induced dilation is mediated by nitric oxide, hypoxia-induced dilation is mediated by prostaglandins, and flow-induced dilation is mediated by both.

	COMPLEX PHARMACOLOGY OF THE PULMONARY VASCULATURE

The pulmonary vasculature normally functions in a relatively low tone state, and the pulmonary vasoconstriction associated with certain pulmonary and/or systemic injuries and diseases often appears to be a maladaptive response. Such responses may occur because of the existence of latent mechanisms, the influence of which is normally restrained by more dominant mechanisms. Inappropriate pulmonary vasoconstriction may result from a shift in the balance between such mechanisms. In this issue, we find two examples of apparent shifts in such a balance. In one, Voelkel et al. (p. 1715) report that cyclic nucleotides cGMP and cAMP, which are usually considered to be involved in vasodilatory mechanisms, become vasoconstrictors in rat lungs perfused with small amounts of human hemolysate. They suspect that a low-molecular-weight component of the hemolysate unmasks vasoconstrictor mechanisms of action of the cyclic nucleotides to produce this paradoxical effect. In another study, Maruyama et al. (p. 1687) report that acetylcholine-induced vasodilation is impaired in pulmonary arteries from chronically hypoxic rats. By using prostanoid synthesis and receptor antagonists they obtained evidence that the impaired acetylcholine-induced relaxation may involve the competing influence of an acetylcholine-induced production of a vasoconstrictor prostanoid in the chronically hypoxic vessels. Changes in the balance of such mechanisms may complicate interpretation of experimental results and may also have a role in the pathophysiology of pulmonary hypertension.