Involvement of gamma-aminobutyric acid (GABA) B receptors in the hypotensive effect of systemically administered GABA in spontaneously hypertensive rats.
We investigated the effects of intraduodenally (i.d.) administered gamma-aminobutyric acid (GABA) on blood pressure (BP) in anesthetized spontaneously hypertensive rats (SHR) and the mechanism underlying this effect, especially the type of GABA receptor involved in the depressive effect of this amino acid. GABA (0.3 to 300 mg/kg, i.d.) caused a dose-related decrease in the BP of 9.20 +/- 3.96 to 35.0 +/- 5.34 mmHg (mean +/- S.E.M.) that lasted for 30 to 50 min. The minimum effective i.d. dose of GABA was 0.3 to 1.0 mg/kg. Results pertaining to the mechanism underlying the GABA-induced effects on BP were as follows: a) GABA did not alter the BP-related effects of exogenous noradrenaline and acetylcholine; b) pretreatment with hexamethonium decreased the GABA-induced fall in BP, and GABA tended to reduce the pressor response associated with injection of dimethyl phenylpiperazinium; and c) pretreatment with 2-hydroxysaclofen markedly reduced the GABA-induced drop in BP, whereas pretreatment with bicuculline did not. In conclusion, in SHR, low-dose (0.3 to 1.0 mg/kg, i.d.) GABA had a hypotensive effect, which may result from attenuation of sympathetic transmission through the activation of GABA(B) receptors at presynaptic or ganglionic sites.
Kimura
Masayuki
M
Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo, Japan. masayuki-kimura@yakult.co.jp
Hayakawa
Kazuhito
K
Sansawa
Hiroshi
H
D000818:Animals; D004305:Dose-Response Relationship, Drug; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D018080:Receptors, GABA-B / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000627:therapeutic use*
D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid