Endothelin-1 in Rat Periaqueductal Gray Area Induces Hypertension Via Glutamatergic Receptors

Abstract

Abstract We investigated the possible relationship between endothelin-1 injection into the dorsolateral periaqueductal gray area and the glutamatergic system in the control of cardiovascular function. Endothelin-1 was injected into the dorsolateral periaqueductal gray area of freely moving rats at doses ranging from 0.1 to 10 pmol. Endothelin-1 increased arterial blood pressure (from 7.0±1.6 to 55.0±4.1 mm Hg, mean±SEM) in a dose-dependent manner and induced characteristic behavioral changes such as longitudinal rolling of the body (barrel-rolling). dl -2-Amino-5-phosphonovaleric acid and (5 R ,10 S )-(+)-5-methyl-10,11-dihydro-5 H -dibenzo[ d -α]cyclohepten-5,10-imine hydrogen maleate, both selective N -methyl- d -aspartate excitatory amino acid receptor antagonists, but not 6-cyano-7-nitroquinoxaline-2,3-dione, a non– N -methyl- d -aspartate excitatory amino acid receptor antagonist, significantly decreased endothelin-1–induced cardiovascular and behavioral changes ( P <.01). Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, also prevented these effects. We propose that the glutamatergic system may exert, via N -methyl- d -aspartate receptors, a significant influence on endothelin-1–induced cardiovascular and behavioral effects after its injection into the periaqueductal area.