Endothelin-1 modulates cardiorespiratory control by the central nervous system

In urethane-anesthetized, vagotomized and immobilized rats under artificial ventilation, an intracisternal injection of 0.1 pmol of endothelin-1 resulted in immediate increases, lasting for 3-15 min, in arterial pressure, heart rate and renal sympathetic nerve activity. Phrenic nerve activity and the rate of its burst activity (burst rate) also increased initially but subsequently decreased for 5-20 min. At doses of 1 or 10 pmol, the initial increases (phase I) were followed by a period of decreases in all variables, that lasted for 20-80 min, below the pre-injection level (phase II). Phrenic nerve activity often disappeared completely. All the variables usually returned to, or often exceeded, pre-injection levels (phase III). However, arterial pressure sometimes remained below control for at least 2 h. Topical application of endothelin-1 to the ventral surface of the medulla produced the same pattern of changes as with intracisternal injection. This particular response pattern was not generated by local administration to any other brain sites examined. In conclusion, intracisternally administered endothelin-1 modulates cardiorespiratory control by the central nervous system. The effect on the central respiratory control was especially powerful. The ventral surface of the medulla appears to play a crucial role in this modulation.