title: Tonic γ-aminobutyric acid-ergic activity in the hypothalamic arcuate nucleus is attenuated in the spontaneously hypertensive rat.
abstract: We tested the hypothesis that tonic γ-aminobutyric acid-ergic activity in the hypothalamic arcuate nucleus (ARCN) modulates blood pressure control and attenuation of this inhibitory activity contributes to hypertension in the spontaneously hypertensive rats (SHR). Mean arterial pressure (MAP), heart rate (HR), and greater splanchnic nerve activity (GSNA) were recorded in urethane-anesthetized, artificially ventilated, adult male SHR and Wistar-Kyoto rats (WKY). Microinjections of gabazine into the ARCN elicited significantly smaller increases in MAP, HR, and GSNA in baroreceptor-intact SHR compared with baroreceptor-intact WKY. Attenuation of the responses to gabazine in SHR persisted, despite lowering of their baseline MAP to levels of WKY or barodenervation. Microinjections of N-methyl-d-aspartic acid (NMDA) into the ARCN elicited decreases in MAP and GSNA and increases in HR in baroreceptor-intact WKY. However, after microinjections of gabazine into the ARCN, microinjections of NMDA into the same nucleus elicited pressor responses in baroreceptor-intact WKY. In barodenervated WKY, increases in MAP and GSNA were elicited by ARCN stimulation by NMDA and the increases in HR were exaggerated. In baroreceptor-intact SHR, ARCN stimulation by NMDA elicited increases in MAP, GSNA, and HR which persisted, despite lowering of baseline MAP or barodenervation. Increases in MAP and GSNA elicited by ARCN stimulation by NMDA in barodenervated SHR were significantly greater than corresponding increases in barodenervated WKY. These results indicated that attenuated γ-aminobutyric acid-ergic activity in the ARCN and impaired baroreflex function may contribute to increases in blood pressure and sympathetic nerve activity after ARCN stimulation by NMDA and elevation of baseline blood pressure in SHR.
authors.affiliation: Department of Neurological Surgery, MSB H-586, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 S Orange Ave, Newark, NJ 07107-3000, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawabe
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kawabe
authors.forename: Hreday N
authors.initials: HN
authors.lastname: Sapru
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000503:physiopathology*; D062186:Arterial Pressure / Q000187:drug effects; D017704:Baroreflex; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009478:Neuropeptide Y / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D009478:Neuropeptide Y; D011724:Pyridazines; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; C049853:gabazine
keywords: baroreflex; blood pressure; heart rate; hypertension; sympathetic nervous system