GABA_A receptor in the Pedunculopontine tegmental (PPT) nucleus: Effects on cardiovascular system

The pedunculopontine tegmental (PPT) nucleus is a heterogeneous nucleus with several functions including cardiovascular regulation. The presence of GABA_A receptor has been shown in the PPT. Therefore, the cardiovascular effects of this receptor were examined.

Rats were divided into: Control; Muscimol; Bicuculline (BMI); Hexamethonium (Hexa)+BMI and Atropine+BMI groups. The femoral vein and artery were cannulated for drug administration and recording of cardiovascular parameters, respectively. Muscimol (a GABA_A agonist; 1.5 and 2.5nmol), BMI (a GABA_A antagonist; 0.1 and 0.2nmol) were stereotaxically microinjected into the PPT. To evaluate the peripheral cardiovascular mechanisms of GABA_A receptors, Hexa (a ganglionic blocker; 10mg/kg) and atropine (a muscarinic receptor antagonist; 1mg/kg) were intravenously (iv) injected before BMI (0.2nmol). The average changes of mean arterial pressure (ΔMAP), systolic blood pressure (ΔSBP) and heart rate (ΔHR) in different intervals were calculated and compared both within and between case group and control group (repeated measures ANOVA). The peak changes in each group were also calculated and compared with those of the control group (independent sample t-test).

Both doses of BMI significantly increased ΔMAP, ΔSBP and ΔHR compared to control, while the only higher dose of muscimol significantly decreased ΔSBP. Iv injection of Hexa significantly attenuated ΔMAP, ΔSBP and ΔHR responses induced by BMI but atropine did not affect.

Our results demonstrate that GABA_A receptor of the PPT has a tonic inhibitory effect on the cardiovascular system and its peripheral effect mostly is mediated by sympathetic system.