IS INCREASED PULMONARY VASCULAR PERMEABILITY AFTER HYPERINFLATION AN ACTIVE CELLULAR RESPONSE?

Hyperinflation of the lungs can cause increases in pulmonary vascular permeability. This has been explained mainly by passive stretching of pores and/or stress failure, resulting in breaks in the endothelium due to the primary mechanical forces involved. However, Parker et al. (p. 1113) have considered the possibility that there may be an additional, active component to this phenomenon. Their hypothesis is that the primary mechanical stress, such as high transpulmonary pressure, also results in the influx of calcium into the endothelial cells through stretch-activated calcium channels. According to this hypothesis, the increased intracellular calcium could increase cytoskeletal tone, such that the cells actively pull themselves apart. To evaluate this hypothesis, Parker et al. examined the effect of gadolinium, a stretch-activated calcium-channel blocker, on the increase in capillary filtration coefficient that occurs in isolated perfused rat lungs exposed to high peak inflation pressures. The gadolinium treatment was quite effective in preventing the increase in capillary filtration coefficient, consistent with the hypothesis that there is an active component to the endothelial response to stretch. The paper is discussed in an Invited Editorial by Curry (p. 1111).

	VENTILATORY INHIBITION BY DOPAMINE

Loos et al. (p. 1131) investigated the roles of the carotid chemoreceptors and extracarotid chemoreceptor mechanisms in determining the hypoventilation induced by exogenous dopamine (DA) infusion. Using a combination of carotid sinus nerve recordings, along with hyperoxia and baro- and chemodenervation in the anesthetized cat, they showed that the hypoventilation attending low-dose DA was entirely attributable to its influence on the carotid chemoreceptor. However, with high-dose DA, the hypoventilatory response persisted after carotid body and carotid baroreceptor denervation and was closely correlated with a concomitant increase in systemic blood pressure. Only blockage of the attending vasoconstriction blocked the ventilatory response. These data strongly implicate an important role for the peripheral circulation and possibly type III-IV muscle receptors in the control of breathing.

	WOOD SMOKE INHIBITS PULMONARY STRETCH-RECEPTOR DISCHARGE

Pulmonary exposure to wood smoke results in a complex series of respiratory responses, reflecting alterations in the behavior of bronchopulmonary receptors. Lai and Kou (p. 1138) examined the responses of slowly adapting pulmonary stretch receptors (PSRs) to wood smoke exposure in anesthetized rats. The predominant response was inhibition of receptor discharge. This response could be mimicked by exposure to 15% CO₂ (about the concentration present in wood smoke) and could be prevented by pretreatment with acetazolamide. The results are consistent with the hypothesis that inhibition of PSR discharge by wood smoke is due to the contained CO₂ and that the response reflects acidification of the receptors by carbonic anhydrase catalyzed hydration of CO₂.

	CATECHOLAMINE RESPONSES IN WOMEN EXPOSED TO HIGH ALTITUDE

Acclimatization to high altitude is known to include a sympathoadrenal response in men, with increased catecholamine excretion in the urine. Mazzeo et al. (p. 1151) conducted a study to see whether a similar response to high-altitude exposure occurs in women and, if so, whether it is influenced by the reproductive cycle. Eumenorrheic women were studied at sea level and during a 12-day stay on the summit of Pikes Peak (4,300 m). Urinary norepinephrine excretion increased and remained elevated throughout the high-altitude exposure. Urinary epinephrine excretion also rose but then returned toward sea-level values by day 3. These responses were similar in the follicular and luteal phases of the reproductive cycle. Thus the sympathoadrenal responses in women are similar to those previously documented in men.

	PULMONARY VASCULAR INTEGRITY IS MAINTAINED DURING SUBMAXIMAL EXERCISE

Gross or microscopic pulmonary hemorrhage has been shown to occur during all-out exercise in several species of mammals, including humans. Bronchoalveolar lavage fluid, obtained from elite cyclists after 6-8 min of maximal exercise, contains increased concentrations of red blood cells, total protein, and leukotriene B₄ (LTB₄), presumably reflecting compromise of the pulmonary microvascular barrier by the high intravascular pressures associated with maximal exercise. Hopkins et al. (p. 1185) performed a similar study, obtaining bronchoalveolar lavage fluid from cyclists after 1 h of heavy but submaximal work. The concentrations of red blood cells, protein, and LTB₄ were no different from those in fluid from control subjects. The authors conclude that exercise-induced disruption of the pulmonary blood-gas barrier occurs only at extreme levels of exercise.

	POLYCYTHEMIC RESPONSES TO HYPOXIA: MOLECULAR AND GENETIC MECHANISMS

Ou and associates (p. 1242) have addressed the mechanisms underlying the markedly divergent polycythemic response to residence at high altitude, as manifested by the markedly different responses in two rat strains. The dose-response relationship of erythropoietin gene expression to renal tissue hypoxia was similar in the two strains; however, the more polycythemic rats showed impaired pulmonary O₂ transport and, therefore, greater systemic arterial hypoxemia and more marked renal tissue hypoxia. The regulation of erythropoietin production in hypoxia occurs primarily at the transcriptional level.

	EXERCISE REDUCES BONE LOSS DUE TO DIETARY WEIGHT LOSS IN POSTMENOPAUSAL WOMEN

Ryan et al. (p. 1305) examined the consequences of 6 mo of weight loss (WL) by caloric restriction, with and without aerobic exercise (AEx), on bone mineral density (BMD) in healthy postmenopausal women who were not taking hormone replacement. Total body BMD decreased in both groups. Regional femoral BMD decreased in the women undergoing WL alone but not in those undergoing WL plus AEx. The outcome suggests that adding exercise to weight-loss programs may reduce the risk of bone loss in postmenopausal women.

	METABOLIC AND HEMODYNAMIC CONSEQUENCES OF DETRAINING

Endurance exercise training results in greatly improved insulin action, and inactivity results in the opposite effect. Much less is known about the hemodynamic effects of insulin in trained and detrained muscle. Arciero et al. (p. 1365) measured blood glucose and insulin responses and arm and calf blood flow rates after an oral glucose load in endurance-trained men before and after 7-10 days of detraining. After detraining, glucose and insulin rose more, and calf, but not arm, blood flow tended to fall. These results suggest that the purported hyperemic effects of insulin are modulated by endurance training.

	RESPIRATORY CONSEQUENCES OF BED SHARING

Some infants customarily sleep in their mothers' beds, whereas others sleep by themselves. Do these different practices, determined by a host of cultural and economic variables, have respiratory consequences? Richard et al. (p. 1374) compared the frequencies of central and obstructive apneas and of periodic breathing in healthy infants during 2 nights in a sleep laboratory. Each child spent 1 night bed sharing with the mother and 1 night sleeping alone. Both routinely bed- sharing and routinely solitary infants had more central apneas and periodic breathing while bed sharing in the laboratory setting. The routinely solitary sleepers had fewer obstructive apneas while bedsharing in the laboratory. The mechanisms remain obscure, but the results indicate an influence of bed sharing on respiratory behavior during sleep.