Sites and mechanism of action for the effects of intrathecal noradrenaline on thermoregulation in the rat.

1. In unanaesthetized rats, intrathecal injection of 0.30 mumole noradrenaline (NA) at the level of the lumbar enlargement produced a transient rise in core temperature followed by prolonged hypothermia and tail skin vasodilation.2. Studies of the distribution of [(3)H]NA injected at the lumbar enlargement revealed that at least 97% of the activity recovered from the central nervous system was located in the spinal cord, primarily within the thoracic and upper lumbar segments. Thus, the thermoregulatory effects of intrathecal NA are not likely to be due to an action at supraspinal sites.3. Studies with [(3)H]NA also indicated that significant levels of unmetabolized labelled NA were present in plasma as early as 3 min after intrathecal injection. However, by 15 min after injection, 75% of this radioactivity had disappeared. There was a good temporal correlation between the transient appearance of high levels of NA in plasma and the initial hyperthermic effect of NA. Moreover, the hyperthermia was not inhibited by mecamylamine-induced ganglionic blockade. These results indicate that the initial hyperthermic effect of intrathecal NA is due to a direct action of this monoamine at peripheral sites subsequent to leakage from the spinal subarachnoid space.4. In anaesthetized rats, NA (0.30 mumole) and clonidine (0.035 mumole) injected intrathecally at the lumbar enlargement produced a sustained decrease in neural activity recorded from the lumbar sympathetic chain, a finding which suggests that the vasodilation and hypothermia produced by intrathecal NA are due to an inhibition of sympathetic outflow.5. To investigate the spinal site of action of NA on thermoregulation, rats were prepared with spinal catheters which extended either to the upper cervical region or the lower sacral area. Studies with [(3)H]NA showed that these modifications of the catheter lengths altered the accessability of NA to the intermediolateral nucleus (i.m.l.) of the spinal cord. Injections of NA through the cervical and sacral catheters elicited thermoregulatory effects which differed from those elicited by injections near the lumbar enlargement. The differences were consistent with the hypothesis that the hypothermia and tail skin vasodilation elicited by NA injected at the lumbar enlargement are mediated, at least in part, via a direct inhibitory effect of this monoamine on sympathetic preganglionic neurones located in the i.m.l.6. The effect on mean arterial blood pressure of intrathecal injection of NA (0.30 mumole) at the lumbar enlargement was examined in unanaesthetized rats fitted with chronic arterial catheters. These injections produced an immediate increase in blood pressure. However, this effect was transient and, during most of the time when NA-induced vasodilation and hypothermia were present, blood pressure was normal or only slightly elevated. Thus, it is not likely that a baroreceptor-mediated reflex inhibition of sympathetic outflow contributed significantly to the vasodilatory or hypothermic action of NA.