EFFECTS OF LONG-TERM ORAL-ADMINISTRATION OF NZ-105, A NOVEL CALCIUM-ANTAGONIST, WITH OR WITHOUT PROPRANOLOL IN SPONTANEOUSLY HYPERTENSIVE RATS

A new calcium antagonist, NZ-105 ((+/-)-2-[benzyl(phenyl)amino]ethyl i nan-2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethano l) (10 mg kg-1, p.o.), showed slow-onset hypotensive effect in spontan eously hypertensive rats (SHRs). The tachycardia evoked by NZ-105 was completely prevented when combined with a beta-adrenoceptor blocker, p ropranolol (20 mg kg-1), which did not affect the hypotensive response to NZ-105. In long-term administration experiments for 12 weeks with SHRs, the systolic blood pressure in the control group increased with age and the heart was stable throughout the period. NZ-105 (10 mg kg-1 day-1) alone and its combined treatment with propranolol (20 mg kg-1 day-1) maintained the systolic blood pressure and heart rate at a low level compared with the control group. The hypotensive action of NZ-10 5 was reproducible after repeated dosing for 12 weeks. Long-term admin istration of propranolol affected neither the elevation of the systoli c blood pressure nor the heart rate substantially. The heart weight pe r body weight was significantly reduced after the chronic combination of both drugs, suggesting that the cardiac hypertrophy accompanying hy pertension was prevented.