TY - JOUR
AU - Yen, Mao-Hsiung
AB - The hypotensive effect of DC-015, a newly synthesized quinazoline derivative,was investigated and compared with prazosin in spontaneously hypertensiverats (SHR). Intravenous administration of DC-015 and prazosin (both at 0.01,0.05 and 0.1 mg/kg) induced a dose-dependent reduction of mean arterial pressure(MAP) which reached a maximal effect at 5 min after injection and persistedover 2 h in SHR. Furthermore, at higher doses DC-015 (0.1 mg/kg i.v.and 2.0 mg/kg orally, respectively) did not cause any significant changes inheart rate (HR); whereas the same doses of prazosin (0.1 mg/kg i.v. and 2.0 mg/kg orally, respectively) produced a decrease in HR which seems to parallel thetime course of the hypotensive response in SHR. DC-015 and prazosin attenuatedpressor responses to phenylephrine (10 μg/kg) but failed to inhibit the pressoreffects of angiotensin II (0.5 μg/kg) even at the maximal hypotensive dose(0.1 mg/kg). This observation indicates that DC-015 appears to exert its hypotensiveeffect through α(1)-adrenoceptor blockade. On the other hand, in SHR feda high-fat-high-cholesterol (HF-HC) diet, oral administration of DC-015 andprazosin (both at 1.0 mg/kg, twice a day) for 4 weeks caused significant reductionsin total plasma cholesterol (CE), low-density lipoprotein (LDL)-cholesteroland total plasma triglyceride (TG). DC-015 therapy also increased high-densitylipoprotein (HLD)-cholesterol levels, thus the ratio of total plasma cholesterolto HDL-CE was improved. In contrast, prazosin did not significantlyincrease the HDL-CE level in this study. It is concluded that DC-015 decreasedMAP, plasma CE, LDL-CE, plasma TG and increased HDL-CE levels. DC-015may have therapeutic potential as a potent antihypertensive drug via the α(1)-adrenoceptorantagonist. Concurrently, DC-015 may thus hold some advantagefor the reduction of two of the major risk factors, hypertension and hyperlipidemia,for cardiovascular diseases.
TI - Antihypertensive and Hypolipidemic Effects of DC-015, a Novel, Potent and Specific α(1)-Adrenoceptor Antagonist: Comparison with Prazosin in Spontaneo ...
JF - Journal of Biomedical Science
DO - 10.1159/000456905
DA - 2017-01-01
UR - https://www.deepdyve.com/lp/karger/antihypertensive-and-hypolipidemic-effects-of-dc-015-a-novel-potent-0IwsDk30AG
SP - 108
EP - 116
VL - 3
IS - 2
DP - DeepDyve
ER -