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.
Hashim
M A
MA
Division of Pharmacology, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
Tadepalli
A S
AS
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007022:Hypotension; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*
D016232:Endothelins; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate