Antihypertensive effect of synthetic tetrandrine derivatives in SHR rats.
1. Effects of oral administration of synthetic tetrandrine (TD) derivatives (20 mg/kg per day) for 9 weeks on blood pressure, heart rate, plasma renin concentration (PRC) and vascular reactivities to pressor substances were studied in spontaneously hypertensive (SHR) rats. 2. 7-O-Ethyl fangchinolin (7-O-EFC) and 7-O-isopropyl fangchinolin (7-O-IFC) produced a significant and sustained reduction in blood pressure from the first week of administration. 7-O-EFC reduced heart rate when determined under restraint conditions, but not under unanesthetized, freely moving conditions. 3. TD derivatives produced no effect on PRC. 4. Pressor response to phenylephrine was reduced significantly whereas the response to angiotensin II was enhanced after prolonged administration of 7-O-EFC and 7-O-IFC. 5. These results demonstrate that TD derivatives are potential antihypertensive drugs, and that attenuation of the pressor response to phenylephrine may contribute at least in part to its antihypertensive effect.
Kawashima
K
K
Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
Hayakawa
T
T
Oohata
H
H
Fujimoto
K
K
Suzuki
T
T
Ogino
T
T
Chen
Z X
ZX
D000470:Alkaloids / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood
D000470:Alkaloids; D000959:Antihypertensive Agents; D044182:Benzylisoquinolines; D000804:Angiotensin II; C069407:7-O-ethyl fangchinoline; C069425:7-O-isopropyl fangchinoline; D010656:Phenylephrine; C009438:tetrandrine; D009529:Nicardipine; D012083:Renin