NMDA receptor and NO mediate ET-1-induced behavioral and cardiovascular effects in periaqueductal gray matter of rats

Abstract

Endothelin-1 (ET-1), a novel and potent vasoconstrictor in blood vessel, is known to have some functions in the rat central nervous system (CNS). In order to investigate the central functions of ET-1, ET-1 was administered to the periaqueductal gray area (PAG) of anesthetized rats to induce barrel rolling and increase the arterial blood pressure (ABP). ET-1 had a modulatory effect on central cardiovascular and behavioral control. The selective N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (3 mu mol/kg, i.p.) blocked the ET-1 induced responses, and both the nitric oxide synthase (NOS) inhibitor L-NAME (N-nitro-L-arginine methylester 1 mmol/rat) and the nitric oxide (NO) scavenger hemoglobin (15 nmol/rat) had similar effects in reducing the ET-1 (10 pmol/rat)-induced behavioral changes and ABP elevation. However, NO donor sodium nitroprusside (SNP 10 mug, 1 mug/rat) decreased the ET-1 induced ABP elevation, and recovered the ET-1-induced barrel rolling effect that was reduced by MK-801. These results suggest that ET-1 might have neuromodulatory functions such as ABP elevation and barrel rolling induction in the PAG of the rats via the NMDA receptor and NO.