Blood pressure reduction combining baroreflex restoration for stroke prevention in hypertension in rats

Abstract

Blood pressure reduction is an important and effective strategy in stroke prevention in hypertensives. Recently, we found that baroreflex restoration was also crucial in stroke prevention. The present work was designed to test the hypothesis that a combination of blood pressure reduction and baroreflex restoration may be a new strategy for stroke prevention. In Experiment 1, the effects of ketanserin (0.3, 1, 3, 10 mg/kg), amlodipine (0.3, 1, 2, 3 mg/kg) and their combination (1 + 0.3, 1 + 1, 1 + 2, 1 + 3 mg/kg) on blood pressure and baroreflex sensitivity (BRS) of stroke-prone spontaneously hypertensive rats (SHR-SP) were determined under conscious state. It was found that both amlodipine and ketanserin decreased blood pressure dose-dependently. Ketanserin enfanced BRS from a very small dose but amlodipine enfanced BRS only at largest dose used. At the dose of 1 + 2 mg/kg (ketanserin + amlodipine), the combination possessed the largest synergism on blood pressure reduction. In Experiments 2 and 3, SHR-SP and two-kidney, two-clip (2K2C) renovascular hypertensive rats received life-long treatments with ketanserin (1 mg/kg) and amlodipine (2 mg/kg) or their combination (0.5 + 1, 1 + 2, 2 + 4 mg/kg). The survival time was recorded and the brain lesion was examined. It was found that all kinds of treatments prolonged the survival time of SHR-SP and 2K2C rats. The combination possessed a significantly better effect on stroke prevention than mono-therapies. In conclusion, combination of blood pressure reduction and baroreflex restoration may be a new strategy for the prevention of stroke in hypertension.

Keywords: arterial baroreflex; hypertension; prevention; stroke; stroke-prone spontaneously hypertensive rats; two-clip renovascular hypertensive rats; two-kidney.

Figure 1

The effects of a single dose of amlodipine (Aml) and ketanserin (Ket) or combination on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart period (HP) and baroreflex sensitivity (BRS) in conscious SHR-SP. The values are expressed as mean ± SE. *P < 0.05, **P < 0.01 after drug vs. before drug. n = 9 in each group.

Figure 2

The effects of life-long treatment of ketanserin (Ket) and amlodipine (Aml) on the stroke death in SHR-SP. (A) The survival rate in these six subgroups (G, group), doses referred to Table 1, is expressed by Kaplan-Meier survival curves. (B) The survival time expressed as mean ± SE. *P < 0.05, **P < 0.01, ***P < 0.001 for treatment group vs control group. n = 14–15 in each group. (C) The mortality rate on day 404, when the control rats all died.

Figure 3

The effects of life-long treatment of ketanserin and amlodipine on the stroke death in 2K2C rats. (A) The survival rate in these six subgroups (G, group), doses referred to Table 1, is expressed by Kaplan-Meier survival curves. (B) The survival time expressed as mean ± SE. *P < 0.05, **P < 0.01, ***P < 0.001 for treatment group vs control group. n = 12–15 in each group. (C) The mortality rate on day 344, when the control rats all died.