Hypotension to central endothelin-1: effect of glutamate receptor blockade

Endothelin-1 (ET-1) produces hypotension via an action at glutamate-sensitive medullary cardiovascular sites. Here, we used excitatory amino acid (EAA) receptor antagonists to examine the possible role of an endogenous EAA in this neural action of central ET-1. ET-1 (3 pmol) applied to the IV ventricle of anesthetized, artificially ventilated rats elicited a sustained decrease in blood pressure (27 +/- 6%). Pretreatment with two EAA receptor antagonists, APV and CNQX (or MK-801 and CNQX), significantly attenuated the hypotension to central ET-1 (11 +/- 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.