Correlation between neural release of VIP and adrenomedullary catecholamine secretion in vivo

The aim of the present study was to determine whether vasoactive intestinal peptide (VIP) can be released along with catecholamines from the adrenal gland in response to direct splanchnic nerve stimulation in anesthetized dogs. An attempt was made to verify whether VIP was released mainly from chromaffin cells or from the splanchnic nerve terminals. The first group received a supramaximal stimulation (12 V) given on the left splanchnic nerve at three successive frequencies of 0.2, 2, and 20 Hz. The second group received increasing doses of 1,1-dimethyl-4-phenylpiperazinium (DMPP) locally infused into the denervated left adrenal gland. In response to nerve stimulation, adrenal venous catecholamine concentration significantly increased in a frequency-dependent manner, whereas VIP-like immunoreactive substance (VIP-ir) reached a significant level only at the highest frequency. The multiple linear regression analyses revealed that the net increases in adrenal venous catecholamine concentrations were strongly correlated with combined variables of VIP-ir concentration and frequencies, indicating r = 0.915 and 0.949 (n = 42, P < 0.0001) for epinephrine and norepinephrine concentrations, respectively. In response to local DMPP infusion, adrenal venous catecholamines increased in a dose-dependent manner, whereas VIP-ir remained unchanged. The results indicate that VIP-ir is released along with catecholamines from the dog adrenal gland in response to direct splanchnic nerve stimulation in vivo. The study also suggests that VIP is mainly released from splanchnic nerve endings.