Effect of the substance P antagonist spantide on adrenal sympathetic nerve activity in rats

In order to elucidate the role of substance P in adrenal nerve activity, the effects of substance P antagonists on tonic activity of the adrenal sympathetic nerve, the response to exogenous substance P and cutaneo-adrenal nerve reflex were investigated in anesthetized rats. Substance P or its antagonist [(Arg1, D-Trp7,9, Leu11)-substance P: spantide] was injected into the subarachnoid space via polyethylene tubing. Intrathecal administration of spantide (0.1-10 micrograms) produced a slight and transient increase in tonic activity of the adrenal nerve. Thereafter, a marked and prolonged decrease in adrenal nerve activity was observed, along with a decrease in arterial blood pressure. Intrathecally administered substance P (0.1-10 micrograms) produced a marked increase in tonic activity of the adrenal nerve in a dose-related manner. This substance P-induced increase in adrenal nerve activity was significantly antagonized by pretreatment with spantide. It was also found that spantide depressed the reflex response in adrenal nerve activity evoked by noxious mechanical pinching of the skin. These findings suggest the possibility that on the spinal level, substance P has an important role in the maintenance of tonic activity of the adrenal nerve and the transmission of nociceptive information to the adrenal nerve in rats.