HYPOTENSION TO CENTRAL ENDOTHELIN-1 - EFFECT OF GLUTAMATE-RECEPTOR BLOCKADE

Endothelin-1 (ET-1) produces hypotension via an action at glutamate-se nsitive medullary cardiovascular sites. Here, we used excitatory amino acid (EAA) receptor antagonists to examine the possible role of an en dogenous EAA in this neural action of central ET-1. ET- I (3 pmol) app lied to the IV ventricle of anesthetized, artificially ventilated rats elicited a sustained decrease in blood pressure (27 +/- 6%). Pretreat ment with two EAA receptor antagonists, APV and CNQX (or MK-801 and CN QX), significantly attenuated the hypotension to central ET-1 (II +/- 4%). Since these antagonists do not interact with endothelin receptors , we conclude that release of an endogenous EAA may contribute to the hypotensive action of central ET-1. (C) 1994 Academic Press, Inc.