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.

Characteristic Enhancement of Blood Pressure V-Shaped Waves in Sinoaortic-Denervated Rats in a Conscious and Quiet State

“…BP and heart rate were continuously recorded in conscious, freely moving rats as previously described (Liu et al 2013, Yu et al 2013, Shang et al 2011. Briefly, 4 weeks after SAD or sham operations, rats were anesthetized with pentobarbital sodium and a floating catheter (PE10; Biotrol, Paris, France) was inserted into the lower abdominal artery via the left femoral artery; another catheter (PE50) was inserted into the left femoral vein for intravenous injection.…”

“…After a 14 h habituation, beat-to-beat BP and heart period (HP) values were acquired online for 24 h. Offline analysis was performed to obtain related hemodynamic parameters. The beat-to-beat BP mean values were used as indexes of BP and the standard deviations of beat-tobeat BP values as indexes of BPV (Liu et al 2013, Yu et al 2013, Shang et al 2011.…”

Blood Pressure Variability: Prognostic Value and Therapeutic Implications

“…By multiple regression analysis, Shang et al have found that the reduction in BPV induced by the chronic administration of irbesartan and amlodipine contributes to ameliorate left ventricular hypertrophy and renal lesion in spontaneously hypertensive rats [74]. In another report, the effect of chronic administration of different antihypertensive drugs on target organ damage was studied in spontaneously hypertensive rats.…”

Emerging drugs for autonomic dysfunction in Parkinson's disease

“…Ghrelin, a neuropeptide originally known for its growth hormone-releasing and orexigenic properties and which exerts important pleiotropic effects on the cardiovascular system, has also been shown to increase baroreflex gain in healthy individuals [51]. Particular combination of known antihypertensives can also sensitize baroreflex, probably following blood pressure reductions [52].…”