Ozone-induced alteration in beta-adrenergic pharmacological modulation of pulmonary macrophages.

Ozone is a ubiquitous air pollutant which can affect numerous function s of the respiratory system. However, previous work has not provided any information concerning its ability to modulate pharmacological receptors of pulmonary macrophages. This study examined, using a chemiluminescence assay, the beta-adrenergic modulation of pulmonary macrophages harvested from rabbits exposed for 3 hr/day for 5 days to 0.1, 0.3 or 0.6 ppm ozone (O3) or to 3 hr/day for 20 days to 0.1 or 0.3 ppm. Receptor activity was monitored using release of reactive oxygen species (ROS) following administration to the cells of the beta2-receptor agonist, isoproterenol. An O3-exposure concentration-dependent response was observed for isoproterenol efficacy following 5-day exposures, in that 0.1 ppm O3 induced a significant enhancement of beta-adrenergic inhibition of ROS production, 0.3 ppm ozone produced no significant change from control, and 0.6 ppm decreased inhibition. No significant effects on beta-adrenergic modulation were noted following the 20-day exposures. The results of this study suggest that short-term repeated exposures to O3 are capable of inducing alterations in the pharmacological functioning of pulmonary macrophages, while longer term exposures may result in adaptation. Alterations in receptor function have implications in terms of pulmonary defense and disease.

Vasodilation of rat retinal microvessels induced by monobutyrin. Dysregulation in diabetes.

1-Butyryl-glycerol (monobutyrin) is a simple lipid product of adipocytes with angiogenic activity. Recent studies have shown that the biosynthesis of this compound is tightly linked to lipolysis, a process associated with changes in blood flow. We now present data indicating that monobutyrin is an effective vasodilator of rodent blood vessels using a fluorescent retinal angiogram assay. The vasodilatory activity of monobutyrin is potent (ED50 = 3.3 x 10(-7) M), dose dependent, and stereospecific. Because diabetes represents a catabolic, lipolytic state with numerous vascular complications, we examined the action and regulation of monobutyrin in insulin-deficient diabetic rats. Serum levels of monobutyrin in streptozotocin-induced diabetic rats were greatly elevated compared to normal animals. At the same time, the retinal vessels of the diabetic animals develop a resistance to the vasodilatory activity of monobutyrin. These results demonstrate a role for monobutyrin in the control of vascular tone and suggest a possible involvement in the pathology of diabetes.