Blood pressure elevation caused by inhibition of brain glutathione reductase

The effect of brain glutathione reductase activity on blood pressure regulation was investigated. The intravenous administration of the glutathione reductase inhibitor, nitrofurantoin (0.1-0.3 mg/rat), to seven normotensive Wistar rats caused dose-dependent rises in blood pressure and the heart rate (delta mean blood pressure 17 +/- 1 mmHg; delta heart rate 89 +/- 7 beats/min for 0.3 mg). Rats treated with 0.3 mg nitrofurantoin showed a 50% decrease in glutathione reductase activity with a twofold increase in the ratio of glutathione disulphide to reduced glutathione in the hypothalamus and brainstem, and a 1.5-fold increase in plasma noradrenaline and plasma renin activity compared with controls. These nitrofurantoin-induced effects were totally abolished by pretreatment with a sympathetic ganglion blocker (4 mg pentolinium tartrate, administered subcutaneously) except for the increased ratio of glutathione disulphide to reduced glutathione and the decreased glutathione reductase activity in the brain. These results suggest that the blood pressure elevation caused by inhibition of brain glutathione reductase activity occurs through activation of the sympathetic nervous system and the renin-angiotensin system.