Mechanism underlying gamma-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats.
We examined the effects of gamma-aminobutyric acid (GABA) on the blood pressure in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. A single oral administration (0.5 mg/kg) significantly lowered the systolic blood pressure in spontaneously hypertensive rats, but not in normotensive rats. In the mesenteric arterial bed, the perivascular nerve stimulation-induced increase in perfusion pressure and noradrenaline release were significantly inhibited by GABA in spontaneously hypertensive rats, but not in normotensive rats, and attenuated by the selective GABA(B) receptor agonist, baclofen, but not by the selective GABA(A) receptor agonist muscimol. The inhibitory effects of GABA on the perivascular nerve stimulation-induced increase in perfusion pressure and noradrenaline release were completely antagonized by the selective GABA(B) receptor antagonist, saclofen, but not by the selective GABA(A) receptor antagonist, bicuculline. These results suggest that, in spontaneously hypertensive rats, GABA has an antihypertensive effect due to its inhibition of noradrenaline release from sympathetic nerves in the mesenteric arterial bed via presynaptic GABA(B) receptors.
Hayakawa
Kazuhito
K
Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan. kazuhito-hayakawa@yakult.co.jp
Kimura
Masayuki
M
Kamata
Katsuo
K
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013599:Systole; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000959:Antihypertensive Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D014662:Vasoconstrictor Agents; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D008729:Methoxamine; C080629:saclofen