Synergism of hydrochlorothiazide and nifedipine on blood pressure variability reduction and organ protection in spontaneously hypertensive rats.
This study was designed to investigate the effects of a hydrochlorothiazide-nifedipine combination on blood pressure (BP), blood pressure variability (BPV), baroreflex sensitivity (BRS), and organ protection in spontaneously hypertensive rats (SHR). The doses used were 10 mg/kg/d for both hydrochlorothiazide and nifedipine, and 10+10 mg/kg/d for the combination of these two drugs. Drugs were mixed into rat chow at the aforementioned doses. SHR were treated for 4 months, and then BP was continuously recorded for 24 h. After the determination of BRS, rats were killed for organ-damage evaluation. It was found that long-term treatment with hydrochlorothiazide, nifedipine or both significantly decreased BP and BPV, enhanced BRS and conferred organ protection in SHR. The combination of hydrochlorothiazide and nifedipine had a significant synergistic effect on BPV reduction, BRS enhancement and organ protection in SHR, whereas no obvious synergism on BP reduction was found. Multiple-regression analysis showed that the decrease in left ventricular and aortic hypertrophy was most closely associated with the decrease in systolic BPV and the increase in BRS, and the amelioration of renal lesions was most closely associated with the increase in BRS. In conclusion, long-term treatment with a combination of hydrochlorothiazide and nifedipine yielded a significantly synergistic effect on BPV reduction, BRS restoration and organ protection in SHR. In addition to BP reduction, the decrease in BPV and the enhancement of BRS may have made important contributions to the observed organ protection.
Xie
He-Hui
HH
Department of Pharmacology, Second Military Medical University, Shanghai, P.R.China.
Zhang
Xiao-Fei
XF
Chen
Yuan-Yuan
YY
Shen
Fu-Ming
FM
Su
Ding-Feng
DF
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004357:Drug Synergism; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D006977:Hypertension, Renal / Q000150:complications* / Q000188:drug therapy*; D016014:Linear Models; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D006852:Hydrochlorothiazide; D009543:Nifedipine