Comparison study on antihypertensive drugs for treatment of pre-hypertension in rats

Background: Pharmacological treatment from pre-hypertension may benefit to long-term blood pressure and target organ. Purpose: To compare the effects of losartan and amlodipine on systolic blood pressure (SBP) and brain for treatment of pre-hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). Methods: SHRSP were administered with losartan (6 or 16 weeks, respectively), amlodipine (6 or 16 weeks, respectively) or saline from pre-hypertension. Wistar-Kyoto rats were used as a control. Rats were followed up until 40-weeks-old. SBP was determined by tail-cuff method. Stroke was determined with the clinical score of stroke and optical microscope. Apoptosis was analyzed by electron microscopy and TdT-mediated dUTP-biotin nick end labeling. Protein expressions of gp91phox, superoxide dismutase (SOD), and angiotensin II type 1 (AT1R) and type 2 (AT2R) receptor in the cerebral cortex were detected by western blot. Results: The progressions of BP were more slowly in losartan treated SHRSP. Compare with amlodipine, losartan further improved structure and morphology of brain, decreased the clinical score of stroke, and reduced stroke. However, amlodipine showed superior in delaying the peak of apoptosis. Losartan further decreased the protein expression of AT1R and increased the protein expression of AT2R but amlodipine further decreased the protein expression of gp91phox and increased the protein expression of SOD. Longer administration, much effects. Conclusions: Treatment with losartan from pre-hypertension is more effective than amlodipine on delaying long-term BP increase, ameliorating cerebral structure, and reducing stroke due to its stronger inhibition of AT1R and activation of AT2R. However, amlodipine shows superior in delaying the peak of apoptosis because of its stronger anti-oxidative stress.