Role of metabotropic glutamate receptors in ventrolateral medulla of hypertensive rats.
Evidence is accumulating for the role of metabotropic, as well as ionotropic, glutamate receptors in cardiovascular regulation. We sought to determine whether stimulation of metabotropic glutamate receptors in the rostral ventrolateral medulla would evoke enhanced cardiovascular responses in spontaneously hypertensive rats (SHR). Thus, we microinjected (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], a selective agonist of metabotropic glutamate receptors, into the rostral ventrolateral medulla of urethane-anesthetized adult SHR and age-matched Wistar-Kyoto (WKY) rats. Microinjection of (1S,3R)-ACPD (1 nmol/50 nL) produced increases in mean arterial pressure and splanchnic sympathetic nerve activity in SHR (+41 +/- 6 mm Hg and +34 +/- 4%, respectively) that were significantly greater than those observed in WKY rats (+18 +/- 3 mm Hg and +22 +/- 3%, P < .005 and P < .05, respectively). The pressor responses evoked by microinjection of L-glutamate (2 nmol), N-methyl-D-aspartate (20 pmol), or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (5 pmol) were also significantly (P < .001) augmented in SHR (+55 +/- 3, +61 +/- 7, and +53 +/- 5 mm Hg, respectively, in SHR versus +31 +/- 1, +30 +/- 3, and +28 +/- 2 mm Hg in WKY rats). Results indicate that stimulation of metabotropic, as well as ionotropic, glutamate receptors in the rostral ventrolateral medulla evokes enhanced cardiovascular responses in SHR, which may contribute to hypertension in this model.
Tsuchihashi
T
T
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abe
I
I
Fujishima
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000503:physiopathology*; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid