Activated endothelial cells in culture suppress baroreceptors in the carotid sinus of dog.

Vascular stretch increases the activity of arterial baroreceptors along with the production and release of substances from the endothelium. We hypothesized that endothelial factors modulate the sensitivity of baroreceptors during increases in arterial pressure. Baroreceptor activity was recorded from single fibers innervating the isolated carotid sinus of dogs anesthetized with chloralose after removal of the endothelium (balloon denudation) and after replacing into the denuded sinus bovine aortic endothelial cells cultured on microcarrier beads. The endothelial cells were activated with either the calcium ionophore A23187 (2 microM) or bradykinin (10 microM). The threshold pressure (n = 7) determined with a slow ramp increase in static pressure averaged 73 +/- 7 (SEM) mm Hg during exposure to naked beads and was increased significantly (96 +/- 18 mm Hg; p less than 0.05) during exposure to endothelial cell cultures. During stepwise increases in pressure, activity (n = 6) averaged 14 +/- 5, 40 +/- 8, and 54 +/- 8 spikes/sec at 75, 125, and 175 mm Hg during exposure to naked beads and decreased significantly to 2 +/- 2, 30 +/- 11, and 35 +/- 12 spikes/sec at equivalent pressures during exposure to the cell cultures. The activity was restored after replacement of the cell cultures with naked beads. The suppressed activity was not caused by changes in carotid sinus diameter or strain (sonomicrometers) or by the chemical activators that were also added to the naked beads. The results indicate that chemically activated endothelial cells release an inhibitory factor that suppresses baroreceptor activity.