Effects of Long-term Treatment with Ketanserin on Blood Pressure Variability and End-Organ Damage in Spontaneously Hypertensive Rats

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Abstract
It has been proposed that instability of blood pressure may produce organ damage. Ketanserin is an anti-hypertensive drug with an ability to reduce blood pressure variability (BPV) in acute experiments in spontaneously hypertensive rats (SHRs). The present work was designed to observe the effects of long-term treatment with ketanserin on BPV and end-organ damage in SHRs. Ketanserin was mixed in rat chow at an estimated dose of 10 mg/kg/d. After 5 months of drug administration, BP was continuously recorded in conscious, freely moving rats for 24 h. The heart, kidneys, and abdominal aorta were then isolated and examined by using histologic methods and computer image analysis. In another work, the effects of hydralazine (40 mg/kg/d, for 5 months) on BP, BPV, and organ damage were observed in SHRs. Ketanserin significantly decreased BP and BPV, ameliorated impaired arterial baroreflex function, and significantly prevented the target organs of SHRs from being damaged. This preventive effect was characterized by decrease in left ventricular hypertrophy, diminution of glomerulus damage, and amelioration in vascular lesion. Hydralazine decreased BP but did not lower BPV. No organ protection was found in hydralazine-treated rats. In conclusion, long-term treatment with ketanserin reduced hypertensive organ damage. Lowering BP, decreasing BPV, and ameliorating arterial baroreflex function may contribute together to this effect.