Indomethacin reduces acute baroreceptor resetting in the dog

Abstract

1. The influence of local perfusion of the carotid sinus with the cyclo-oxygenase blocker indomethacin on acute baroreceptor resetting was investigated in anaesthetized dogs. 2. The carotid sinus was isolated and perfused with oxygenated Krebs-Henseleit solution. Single units from the carotid sinus nerve were recorded. The carotid sinus was conditioned with static pressures of 50, 100 and 150 mmHg for 15 min. Following the conditioning period a carotid sinus pressure (CSP)-discharge curve was constructed using static stepwise increases in CSP. 3. Perfusion of the carotid sinus with indomethacin (20 microM) caused an elevation in the threshold at every conditioning pressure (96.8 +/- 4.8 vs. 83.8 +/- 4.1 mmHg for 100 mmHg, P < 0.01; 91.9 +/- 4.7 vs. 70.3 +/- 4.4 mmHg for 50 mmHg, P < 0.01; and 103.5 +/- 4.4 vs. 96.4 +/- 4.1 mmHg for 150 mmHg, P = 0.06, respectively) and a significant reduction in the peak discharge rate at each conditioning pressure (32.0 +/- 4.4 vs. 48.2 +/- 5.5 spikes/s for 100 mmHg, P < 0.01; 32.2 +/- 5.8 vs. 45.8 +/- 5.1 spikes/s for 50 mmHg, P < 0.01; 32.0 +/- 3.7 vs. 51.1 +/- 8.1 spikes/s for 150 mmHg, P < 0.01). The resetting ratio (change in threshold/change in conditioning CSP) for both downward resetting (conditioning CSP from 100 to 50 mmHg) and upward resetting (conditioning CSP from 100 to 150 mmHg) was significantly decreased after indomethacin (0.10 +/- 0.02 vs. 0.27 +/- 0.02 for downward resetting, P < 0.01 and 0.14 +/- 0.03 vs. 0.25 +/- 0.01 for upward resetting, P < 0.01, respectively). 4. Conversely, perfusion of the carotid sinus with arachidonic acid (20 microM) significantly decreased the threshold at each conditioning CSP and increased the peak discharge rate at each conditioning CSP. The resetting ratio was significantly increased after arachidonic acid. 5. There was no change in resting carotid diameter or in the carotid sinus pressure-carotid diameter relationship after indomethacin or arachidonic acid. 6. Removal of the endothelial cells in the carotid area with saponin did not prevent the effects of indomethacin on baroreceptor resetting. 7. These results suggest that prostaglandins have a tonic effect on the activity of the carotid sinus baroreceptor and may play a role in acute baroreceptor resetting.