Reduction of blood pressure variability by combination therapy in spontaneously hypertensive rats

Objective To test the hypothesis that combination therapy might be a powerful tool to reduce blood pressure variability (BPV) in the treatment of hypertension. Methods In chronic studies, male spontaneously hypertensive rats were given drugs in their rat chow for 18 weeks (n = 9 or 10 for each group of rats). Doses were as follows: atenolol (110 mg/kg per day), amlodipine (11 mg/kg per day), a combination of atenolol and amlodipine (2.5 + 0.25, 5 + 0.5, and 10 + 1 mg/kg per day), hydrochlorothiazide (8 mg/kg per day), enalapril (3.2 mg/kg per day), and a combination of hydrochlorothiazide and enalapril (2 + 0.8, 4 + 1.6, and 8 + 3.2 mg/kg per day). In acute studies, drugs were perfused through the left femoral vein in conscious rats. Results In chronic studies, compared with monotherapy, the combinations of two anti hypertensive drugs were more effective in reducing the blood pressure (BP), BPV, and organ damage. The indexes of organ damage were all positively related to BP and/or BPV. In acute studies, the constant infusion of phenylephrine (6.251 per min) markedly increased the BP, but showed no significant effects on BPV. The infusion of a combination of atenolol and amiodipine (62.5 + 6.25 mu g/kg per min) or a combination of hydrochlorothiazide and enalapril (500 + 200 mu g/kg per min) significantly reduced the BP and BPV; moreover, a significant reduction in BPV was still found when the rat's BP was restored to control levels by a concomitant infusion of phenylephrine. Conclusions Combination therapy may be a powerful and useful tool for BPV reduction in the treatment of hypertension. In addition to the BP reduction, the decrease in BPV may contribute significantly to the prevention of organ damage in hypertension.