Barbiturate tolerance and hypersensitivity of arterial smooth muscle.

Experiments were undertaken on rats chronically treated with pentobarbital sodium, 50 mg/kg three times per day for a period of five days, to determine whether excised aortic or venous (portal vein) smooth muscle would demonstrate any change in reactivity to catecholamines or potassium chloride. Although sleeping time was reduced 50% (indicative of tolerance to the barbiturate), mean arterial blood pressure was not affected. Aortic strips, but not portal veins, excised from barbiturate-treated animals exhibited hypersensitivity to both contractile stimulants. Potassium-depolarized calcium-depleted aortic tissue, but not portal venous smooth muscle, from the barbiturate-treated animals contracted to lower concentrations of Ca2+ than did the arterial smooth muscle from the saline-treated control rats. The present observations thus indicate that chronic barbiturate treatment in rats can induce drug supersensitivity of excitable tissue other than one associated with the central nervous system. Our results on arterial smooth muscle could help to shed light on the unexplained rises in arterial blood pressure observed in humans undergoing barbiturate withdrawal.