Chronic effects of a beta-adrenoceptor blocking drug, 4-[3-(tert-butylamino)-2-hydroxypropoxy]-N-methylisocarbostyril hydrochloride (N-696), in hypertensive rats.

4-[3-(tert-Butylamino)-2-hydroxypropoxy]-N-methylisocarbostyril hydrochloride (N-696) is a new beta-adrenoceptor blocking drug with direct vasodilatory activity, and may be classified into the fourth generation. Antihypertensive effects of N-696 were studied for 12 weeks in spontaneously (SHR), two kidney, one clip (CLIP), and deoxycorticosterone-salt (DOC) hypertensive rats. Propranolol (PPL) was used as the reference drug. In indirect blood pressure (BP) determination at the tail, milder prewarming condition was employed to observe antihypertensive effects clearly. Rats were prewarmed in rat holders on a hot plate for 30-60 min. Surface temperature of the hot plate was 35-45 degrees C. N-696 (20 mg/kg per day p.o.) and PPL (100 mg/kg per day, p.o.) treatments significantly decreased heart rate (HR) and maximum BP determined indirectly in SHR rats, even at the early stage of the experiments. These antihypertensive effects were shown also by mean BP determined directly at the 12th week. N-696 and PPL treatments showed no significant antihypertensive effects in CLIP rats, and slight antihypertensive effects in DOC rats. N-696 treatments showed a tendency to decrease plasma renin concentration (PRC) in SHR and DOC rats, whereas PPL treatments significantly decreased PRC in these hypertensive rats. N-696 and PPL treatments prevented nephrosclerosis and vascular lesions in SHR and DOC rats only slightly.