EFFECT OF ACTIVATION OF CENTRAL NERVOUS-SYSTEM SEROTONIN 1A RECEPTORS ON CARDIORESPIRATORY FUNCTION

  • 1 February 1989
    • journal article
    • research article
    • Vol. 248  (2) , 851-857
Abstract
Previous studies indicate that the new antihypertensive drug, urapidil, acts at the ventral surface of the medulla in cats to produce a fall in blood pressure. In addition, urapidil was found in receptor binding studies to have a relatively high affinity for the serotonin 1A receptor. These results suggest that drugs which bind to the serotonin 1A receptor might exert hypotensive effects at the ventral surface of the medulla (VSM). To test this hypothesis, the effects of 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), the prototype drug for activating serotonin 1A receptors, were evaluated for cardiovascular activity after local application to the VSM, 8-OH-DPAT applied bilaterally to the intermediate area of the VSM in a dose of 1 .mu.g/side produced a decrease in mean blood pressure of 60 .+-. 7 mm Hg (P < .05) and a decrease in heart rate of 26 .+-. 4 beats/min (P < .05) (n = 8). Increases in respiratory rate (8 .+-. 1 breaths/1 min) and decreases in tidal volume (13 .+-. 4 ml) also occurred. These changes were associated with a significant increase in respiratory minute volume (130 .+-. 41 ml, P < .05). Similar cardiorespiratory changes were produced by application of another drug with high affinity for the serotonin 1A receptor, namely B695-40, to the intermediate area of the VSM. Intravenous administration of 8-OH-DPAT in a dose of 100 .mu.g/kg mimicked the cardiorespiratory effects of ventral surface application of this agent. WB-4101, a drug thought to block serotonin 1A receptors, abolished the respiratory effects and reduced the cardiovascular effects of 8-OH-DPAT. Finally, serotonin alone applied to the intermediate area produced only slight hypotension, but this effect was accentuated by pretreatment with an antagonist of serotonin 2 receptors. These results indicate that drugs that activate serotonin 1A receptors located at the intermediate area of the VSM produce pronounced cardiorespiratory effects, and suggest that serotonin 1A and serotonin 2 receptors mediate opposite actions of serotonin on blood pressure.