Differential effects of prolonged restraint stress on proenkephalin gene expression in the brainstem.

Enkephalins have been discovered in various regions of the brain involved in cardiovascular regulation. The primary source of plasma Met-enkephalin released in response to stress, appears to be from sympathetic nerves. However, levels of Met-enkephalin are 2-3-fold higher at 2 min versus 30 min of restraint stress. Therefore, the purpose of this investigation was 2-fold; to determine whether proenkephalin gene expression is altered in the brainstem during restraint stress, and whether the magnitude of the change is attenuated with prolonged stress. Proenkephalin mRNA levels were compared in the area postrema (AP), nucleus tractus solitarius (NTS), rostral (RVLM) and caudal ventrolateral medulla (CVLM) following 2 and 30 min of restraint stress. During 2 min restraint stress, there was an approximately 1 fold increase in proenkephalin gene expression in the NTS, CVLM and RVLM with a approximately 50% decrease in the AP. With 30 min restraint stress, the increase in proenkephalin gene expression was maintained in the CVLM and RVLM, however mRNA levels had returned to control levels in the NTS and were approximately 1-fold higher than control in the AP. If the increases of proenkephalin gene expression in the NTS, CVLM and RVLM reflect changes in enkephalinergic neuronal activity in those regions, the alterations in enkephalinergic neuronal activity may be an important regulator of blood pressure homeostasis.