Endothelin-1 in rat periaqueductal gray area induces hypertension via glutamatergic receptors.
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 (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[D-alpha] 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.
D'Amico
M
M
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, II University of Naples, Italy.
Berrino
L
L
Maione
S
S
Filippelli
A
A
Pizzirusso
A
A
Vitagliano
S
S
Rossi
F
F
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D008845:Microinjections; D010487:Periaqueductal Gray / Q000187:drug effects*; D011224:Prazosin / Q000008:administration & dosage; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology
D016232:Endothelins; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D012110:Reserpine; D011433:Propranolol; D011224:Prazosin