Effect of Endothelin on Vasomotor and Respiratory Neurons in the Rostral Ventrolateral Medulla in Rats

1. We have previously shown that intracisternal administration of endothelin-1 (ET-1) elicited cardiorespiratory responses acting on the ventral surface of the medulla oblongata (VSM) subjacent to the rostral ventrolateral medulla (RVLM). In this study, we examined whether vasomotor and respiratory neurons in RVLM participate in above-mentioned responses and whether those neurons respond to direct iontophoretic application of ET-1 and/or an ET-A receptor antagonist, FR139317.2. Unit activity of vasomotor, respiratory, or nociceptive neurons in RVLM was recorded together with arterial blood pressure (AP) and heart rate (HR) in urethane-anesthetized Sprague-Dawley rats.3. Intracisternal administration or topical application of ET-1 (0.1–1 pmol) to VSM caused excitation of the majority of vasomotor neurons (15/18) and respiratory neurons (10/11) but not in nociceptive neurons (0/7). Changes in neuronal activity were in similar time course with corresponding changes in AP and HR. Iontophoretic application of ET-1 to the vicinity of recording neuron caused excitation in 19 of 21 vasomotor neurons without affecting AP nor HR. Remaining two neurons were insensitive to ET-1. FR139317 did not affect basal activity of the vasomotor neurons but inhibited ET-1-evoked excitation. Twenty-four of 40 respiratory neurons were excited and 13 were inhibited by iontophoretic application of ET-1. Five of ET-1-excited respiratory neurons were inhibited by FR139317 alone while six of ET-1-inhibited neurons were not affected by FR139317 alone. In both cases, FR139317 inhibited the effect of simultaneously applied ET-1. Iontophoretic application of ET-1 excited only one out of 10 nociceptive neurons so far tested.4. These results support the view that intracisternally administered ET-1 alters activity of vasomotor and respiratory neurons in the RVLM, at least in part by acting directly on neurons themselves and hence causes systemic cardiorespiratory changes. Majority of vasomotor and respiratory neurons should express ET-A receptors and some respiratory neurons are under tonic excitatory control by ET-1.