title: Synergism of irbesartan and amlodipine on hemodynamic amelioration and organ protection in spontaneously hypertensive rats.
abstract: OBJECTIVE
  To investigate the synergism of low-doses of amlodipine and irbesartan on reduction of blood pressure variability (BPV), amelioration of baroreflex sensitivity (BRS) and organ protection in spontaneously hypertensive rats (SHR).
  
  
  METHODS
  The rats were administered amlodipine (1 mg·kg(-1)·d(-1)) alone, irbesartan (10 mg·kg(-1)·d(-1)) alone, or the combination of the two drugs for 4 months. The drugs were mixed into the rat chow. Blood pressure (BP) was continuously monitored in conscious animals. After the determination of BRS, the rats were killed for morphological evaluation of organ damages.
  
  
  RESULTS
  The combination of low-dose irbesartan and amlodipine had statistically significant synergism on reduction of BP and BPV, amelioration of BRS and organ protection in SHR. Multiple regression analysis showed that the decrease in left ventricular hypertrophy was associated with the decrease in systolic BPV (r=0.665, P<0.01); the decrease in aortic hypertrophy was associated with the increase in BRS (r=0.656, P<0.01); and the amelioration in renal lesion was associated with the increase in BRS (r=0.763, P<0.01) and the decrease in systolic BPV (r=0.706, P<0.01).
  
  
  CONCLUSIONS
  Long-term treatment with a combination of low-doses of amlodipine and irbesartan showed significant synergism on reduction of BP and BPV, restoration of BRS and organ protection in SHR. Besides BP reduction, the enhancement of BRS and reduction of BPV might contribute to the organ protection.
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Shang
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.forename: Cheng-bing
authors.initials: CB
authors.lastname: Yang
authors.forename: Xiao-wen
authors.initials: XW
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Xu
authors.forename: Shou-ting
authors.initials: ST
authors.lastname: Fu
authors.forename: Ding-feng
authors.initials: DF
authors.lastname: Su
authors.forename: He-hui
authors.initials: HH
authors.lastname: Xie
mesh_terms: D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017704:Baroreflex / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000473:pathology; D000077405:Irbesartan; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017311:Amlodipine; D000077405:Irbesartan