Hypoxic Ventilatory Reactivity in Experimental Diabetes

Diabetes, apart from generalized neuropathy and microangiopathy, involves tissue hypoxia, which may drive chronic proinflammatory state. However, studies on the ventilatory control in diabetes are sparse and conflicting. In this study we examined the function and morphology of diabetic carotid bodies (CBs). Diabetes was evoked in Wistar rats with streptozotocin (70 mg/kg, i.p.). The acute hypoxic ventilatory responses (HVR) to 12 and 8 % O(2) were investigated in conscious untreated rats after 2 and 4 weeks in a plethysmographic chamber. CBs were dissected and subjected to morphologic investigations: (1) electron transmission microscopy for ultrastructure and (2) laser scanning confocal microscopy to visualize the microvascular bed in sections labeled with the lectin Griffonia simplicifolia-I (GSI), an endothelial cell marker, and fluorescein isothiocyanate (FITC). All findings were referenced to the normal healthy rats. We found that diabetes distinctly dampened the HVR. At the ultrastructural level, the diabetic CB displayed proliferation of connective tissue and neovascularization deranging the interglomal structure, and lengthening the O(2) diffusion path from capillaries to chemoreceptor cells. The chemoreceptor cells remained largely unchanged. The endothelial cell labeling confirmed the intensive angiopathy and the induction of microvessel growth. We conclude that diabetes hampers the chemical regulation of ventilation due to remodeling of CB parenchyma, which may facilitate chronic hypoxia and inflammation in the organ.