Effects of calcium entry blockers on blood pressure and heart rate in neurogenic hypertensive dogs

Abstract

The hypotensive and negative chronotropic effects of 5 calcium entry blockers (verapamil 200 micrograms/kg IV; diltiazem 300 micrograms/kg IV; nifedipine 5 micrograms/kg IV; nicardipine 50 micrograms/kg IV; and bepridil 5 mg/kg IV) were compared in control normotensive and acute neurogenic hypertensive anaesthetized dogs. Acute neurogenic hypertension was induced by sino-aortic denervation (SAD). In control normotensive dogs, all drugs (except bepridil) induced a slight and transient decrease in blood pressure. Nifedipine and nicardipine increased heart rate whereas the three other drugs remained ineffective. SAD caused a 2-2.5-fold increase in the hypotensive properties of the 5 drugs in dogs. Moreover, the duration of this induced hypotension was longer than in control normotensive animals. In SAD dogs, all calcium entry blockers significantly decreased heart rate. This study indicates that the direct cardiac inhibitory action of calcium channel blockers is modulated by baroreceptor activity in intact animals. The mechanism of the selective action of calcium entry blockers in hypertensive SAD in contrast to normotensive dogs is discussed.