Influence of gamma-aminobutyric acid on the changes of blood pressure in rats

Abstract

This is an attempt to investigate the effect of gamma-aminobutyric acid (GABA), a well-known major inhibitory neurotransmitter in the central nervous system, on the blood pressure response in rats and to elucidate the mechanism of its action. GABA injected into a femoral vein of the rat produced a dose-related fall in blood pressure followed by a secondary pressor response. The depressor response evoked by GABA was clearly blocked by pretreatment with chlorisondamine, diazepam and picrotoxin but was unaffected by atropine, prazosin and debrisoquin. GABA-induced pressor responses were significantly attenuated by pretreatment with prazosin or picrotoxin, while not affected by atropine, diazepam, debrisoquin and chlorisondamine. These experimental data suggest that GABA causes biphasically depressor and pressor responses in rats, and that the hypotensive activity evoked by GABA may be exerted through activation of GABAergic receptors and hypertensive activity due to stimulation of the adrenergic alpha-receptors, which appears to be associated with GABAergic receptors.

Fig. 1.

Effects of GABA on the responses of blood pressure of the rat. Other legends and experimental methods are the same as in Fig. 2.

Fig. 2.

Effects of atropine on GABA-induced changes of blood pressure of the rats. Atropine (3.0 mg/kg) was injected intravenously after obtaining the control values. Ordinate: changes of blood pressure in mmHg. Abscissa: doses of GABA in mg/kg. Numerals in the upper parenthesis indicate the number of animals used in the present work. Vertical bars denote S.E. of mean. Statistical differences were obtained by comparing the what with the corresponding control values.

Fig. 3.

Effects of chlorisondamine on GABA-evoked changes of blood pressure. Chlorisondamine (1.0 mg/kg) was given intravenously after obtaining the control responses. The methods and other legends are the same as in Fig. 2. ^* : P<0.05, ^** : P<0.01

Fig. 4.

Effects of prazosin on GABA-evoked changes of blood pressure. Prazosin (1.0 mg/kg) was given intravenously after obtaining the control values. The methods and other legends are the same as in Fig. 2. ^* : P<0.05. ^** : P<0.01

Fig. 5.

Effects of debrisoquin on GABA-evoked changes of blood pressure. Debrisoquin (3.0 mg/kg) was injected into a femoral vein after obtaining the control responses. The methods and other legends are the same as in Fig. 2.

Fig. 6.

Effects of picrotoxin on GABA-evoked changes of blood pressure. Picrotoxin (1 mg/kg) was administered intravenously after obtaining the control value. The methods of experiment and other legends are the same as in Fig. 2. ^* : P<0.05, ^**P<0.01

Fig. 7.

Effects of diazepam on GABA-evoked changes of blood pressure, diazepam (2.0 mg/kg) was given intravenously after obtaining the control value. The methods and other legends are the same as in Fig. 8.