A rabbit model for evaluation of chlorpromazine-induced orthostatic hypotension

The present study was conducted to develop an experimental model for evaluation of chlorpromazine-induced orthostatic hypotension in rabbits. In addition, the alpha-adrenoceptor blocking effect of chlorpromazine was investigated in isolated rabbit aorta and saphenous vein in comparison with prazosin. Chlorpromazine (0.1 and 1 mg/kg, i.v.) potentiated significantly a decrease in mean blood pressure at 1 min after the onset of head-up tilt in rabbits anesthetized with urethane alone, urethane+alpha-chloralose or nitrous oxide alone, but not in conscious and morphine+urethane+alpha-chloralose-anesthetized rabbits. There was a negative correlation (r=-0.986, p<0.01) between the extent of chlorpromazine-induced orthostatic hypotension and the amplitude of tilt-induced reflex tachycardia before chlorpromazine treatment. Both prazosin and pentolinium elicited orthostatic hypotension under all four anesthetic conditions. The pA2 value for chlorpromazine to antagonize norepinephrine-induced contraction in aorta was significantly larger than that in saphenous vein, whereas prazosin blocked aortic and venous contractions to a similar extent. These results suggest that a rabbit under an anesthesia which impairs tilt-induced reflex tachycardia may be useful for evaluation of orthostatic hypotension by chlorpromazine. The relatively low potential of chlorpromazine to produce orthostatic hypotension may be partly due to its weak venodilating action.