[Nicardipine: experimental antihypertensive action and interactions with the alpha-adrenergic sympathetic system]

The antihypertensive properties of nicardipine have been studied in various experimental models of hypertension. Furthermore, the possible contribution of the nicardipine-alpha-adrenergic system interaction to the drug's antihypertensive effect has been investigated. In the conscious normotensive rat, nicardipine (10 and 30 mg/kg, orally) reduces arterial blood pressure (by about 25%) and increases heart rate; these effects are maximal one hour after drug administration and disappear within 4 to 6 hours. In the renovascular hypertensive rat and in the Grollman hypertensive dog, nicardipine (3 mg/kg, orally) significantly decreases blood pressure. Simultaneously, heart rate is increased in the dog but is not significantly modified in the rat. In the conscious adult spontaneously hypertensive rat (SHR), nicardipine administered either as a bolus, or by intra arterial perfusion (1, 5, 12.5 micrograms/kg/min during 30 min), or orally (10, 30 mg/kg) dose-dependently decreases blood pressure and increases heart rate. In the pithed SHR, nicardipine decreases systemic pressor and regional (kidney, mesentery, hindlimb) vasopressor responses to M7, an alpha 2-adrenoceptor specific agonist, but does not affect those to cirazoline, an alpha 1-adrenoceptor specific agonist. However, there is no evidence for an involvement of this alpha 2-sympathoinhibitory effect in the blood pressure lowering action of nicardipine. In conclusion, in the different investigated experimental models of hypertension, nicardipine exerts a potent but short-lasting antihypertensive effect generally accompanied by a reflex tachycardia and a systemic and regional vascular alpha 2-sympathoinhibitory action.