Synergism of irbesartan and amlodipine on hemodynamic amelioration and organ protection in spontaneously hypertensive rats

Abstract

Aim: 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).

Conclusion: 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.

Figure 1

Representative tracings of systolic blood pressure in conscious spontaneously hypertensive rats. SBP, systolic blood pressure; A, spontaneously hypertensive rats; B, irbesartan-treated rats; C, amlodipine-treated rats; D, combination-treated rats.

Figure 2

Effects of long-term treatment with irbesartan, amlodipine alone and in combination on pathological changes in ventricles, aortae, and kidneys in spontaneously hypertensive rats. SHR, spontaneously hypertensive rats (n=11); Irb, irbesartan-treated rats (n=8); Aml, amlodipine-treated rats (n=9); Irb+Aml, combination-treated rats (n=9); LVW, left ventricular weight; BW, body weight; AW, aortic weight; GSS, glomerulosclerosis score. ^bP<0.05, ^cP<0.01 vs SHR; ^eP<0.05, ^fP<0.01 vs Irb.

Figure 3

Examples of correlation between hemodynamic parameters and organ-damage parameters in treated and untreated spontaneously hypertensive rats. n=37. See Table 1 and Figure 2 for abbreviations.