Antihypertensive and diuretic effects of NZ-105, a novel dihydropyridine derivative.
Studies on the antihypertensive and diuretic actions of NZ-105, a new dihydropyridine derivative, were performed in comparison with nicardipine. NZ-105 and nicardipine (5, 10 and 20 mg/kg, p.o.) dose-dependently decreased systolic blood pressure in three types of experimentally hypertensive rats, including spontaneously hypertensive rats, renal hypertensive rats and deoxycorticosterone acetate-salt hypertensive rats and normotensive Wistar-strain rats. The hypotensive effects were larger in hypertensive rats than in normotensive Wistar rats. The hypotensive actions of NZ-105 were very slow in onset and long-lasting in all models, e.g., the hypotension by NZ-105 (10 mg/kg, p.o.) reached a peak (-52 mmHg) at 3 hr and lasted for more than 9 hr in spontaneously hypertensive rats. The hypotensive action in spontaneously hypertensive rats was reproducible after repeated dosing twice a day for 29 days. The hypotensive action after i.v. injection of NZ-105 (0.1 mg/kg) in spontaneously hypertensive rats was also slow in onset (peak time: 10 min) and long-lasting (more than 120 min). The hypotensive potency of NZ-105 was about the same as that of nicardipine, but the increment in heart rate was smaller than in the case of nicardipine. Both NZ-105 and nicardipine showed diuretic and natriuretic actions in spontaneously hypertensive rats. After repeated administration, these actions of NZ-105 were unchanged, whereas those of nicardipine were reduced. These results suggest that NZ-105 is a useful antihypertensive drug with concomitant diuretic effects.
Masuda
Y
Y
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd., Saitama, Japan.
Takeguchi
M
M
Arakawa
C
C
Sakai
T
T
Hibi
M
M
Tanaka
S
S
Shigenobu
K
K
Kasuya
Y
Y
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone; D004095:Dihydropyridines / Q000494:pharmacology*; D004232:Diuretics; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D006977:Hypertension, Renal / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D004095:Dihydropyridines; D004232:Diuretics; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D003900:Desoxycorticosterone; C066425:efonidipine