Abstract
Recent studies have emphasized that endothelial cells produce mediators which control vascular tone not only in the systemic circulation but also in the cerebral circulation. The aim of the present study was to clarify the role of the endothelium in the cerebral vasodilatory response to hypercapnia. An experimental model for cerebral endothelial injury was prepared using monocrotaline (MCT), a pyrrolizidine alkaloid, which causes endothelial damage to the pulmonary and other vascular systems. The regional cerebral blood flow (r-CBF) was measured by the hydrogen clearance method, being monitored in the right and the left frontal white matter. MCT (240 mg/kg) was infused continuously into the left carotid artery. Endothelium-derived vasodilation by ACh (1.7 μg/kg/min) was tested before and after the MCT administration. The dilatory response to hypercapria was also measured during inhalation of 5% CO2 in air before and after the MCT administration. Following MCT infusion, the endothelium-derived vasodilation in response to ACh in the left frontal white matter was decreased (from 12.7% to -4.4%), but the resting r-CBF did not change significantly (from 30.2 to 29.2 ml/100 g brain/min). The vasodilatory response to hypercapnia also showed a significant decrease in the left frontal white matter (from 2.18 to 0.79%/mmHg). The data obtained suggest that MCT produces functional injury of the vascular endothelium, and the cerebral endothelium may play some role in the vasodilatory response to hypervapnia.
