Long-term treatment with glucocorticoids is associated with mild to moderate hypertension. We reported previously that downregulation of endothelial NO synthase (eNOS) expression and activity is likely to contribute to this increase in blood pressure. In the present study, we tested the effects of dexamethasone on the vasodilation of microvascular arterioles using implanted dorsal skin-fold chambers in anesthetized C57BL/6J mice. Experiments were performed on control mice or on mice treated with dexamethasone (0.1-3 mg/kg of body wt). Endothelium-dependent vasodilation in response to ACh (0.1-10 microM) was reduced by dexamethasone in a dose-dependent fashion. Comparable inhibition was seen in tissues superfused with 30 microM N(G)-nitro-L-arginine methyl ester. In contrast, endothelium-independent vasodilation in response to S-nitroso-N-acetyl-D,L-penicillamine (10 microM) was not influenced by either dexamethasone or N(G)-nitro-L-arginine methyl ester. Levels of eNOS mRNA in murine hearts and NO(2)(-)/NO(3)(-) in serum were suppressed by dexamethasone (down to 63 and 50% of control values, respectively, at 3 mg/kg of body wt) along with a reduction in eNOS protein to 85.6%. Dexamethasone also concentration dependently reduced the expression of the cationic amino acid transporter-1 in murine hearts and cultured endothelial cells. The suppression by dexamethasone of the ACh-induced vasodilation could be partially reversed by dietary L-arginine (50 mg/kg of body wt) and by dietary vitamin C (10 g/kg of diet). We conclude that suppression by dexamethasone of the endothelium-mediated microvascular vasodilation involves several mechanisms including 1) downregulation of eNOS, 2) downregulation of cationic amino acid transporter-1, and 3) generation of reactive oxygen species. The demonstration that L-arginine and vitamin C can partially offset the effects of dexamethasone on microvascular arterioles suggests the potential clinical usefulness of these agents for the reduction of glucocorticoid-induced hypertension.

Distal esophageal sensory nerves were stimulated in 17 anesthetized dogs divided into three age groups to determine the laryngeal, cardiovascular, and respiratory effects. Group I puppies were 5 to 6 weeks of age, group II puppies were 8 to 19 weeks of age, and group III animals were adult dogs. Marked laryngeal adductor activity and laryngospasm were observed in group II puppies, while no or minimal laryngeal adduction was seen in younger puppies and adult dogs. Mean arterial pressure and heart rate increased significantly in groups II and III (P < .005) but remained unchanged in group I animals (P > .4). This response is distinctly different from the laryngeal chemoreflex because central apnea, hypotension, and bradycardia were absent. The afferent limb of the response is mediated by the vagus nerve as bilateral transthoracic truncal vagotomy eliminated the reflex. The laryngeal response observed following stimulation of distal esophageal afferent fibers may be important in the mechanism of apparent life-threatening events (ALTEs) and the sudden infant death syndrome (SIDS) associated with gastroesophageal reflux disease.

No abstract

No abstract