Effects Of Transient Prehypertensive Treatment With Losartan And Amlodipine On Blood Pressure And Stroke In Stroke-prone Spontaneously Hypertensive Rats

Objective To compare the effects of transient prehypertensive treatment with losartanand amlodipine on blood pressure and stroke in stroke-prone spontaneouslyhypertensive rats(SHRSP).Methods Four-week-old-male SHRSP were divided into3groups, treated withlosartan(SHRSP-Los:20mg/kg/d,n=24),amlodipine（SHRSP-Aml：10mg/kg/d,n=24）and saline(SHRSP-Veh,n=24) for6weeks,8age-and sex-matched Wistar Kyoto（WKY）rats were served as control group.Rats were followed up until40weeks afterdrug cessation. Systolic blood pressure(SBP) was measured by tail-cuffmeathod.Recording the clinical score of stroke of SHRSP, Plasma and brainAngⅡand Aldo levels were measured by radioimmunoassay. Brain tissue AT1R andAT2R protein levels were determined by immunoblotting.Results During the period of treatment(4~10weeks),SBP in SHRSP-Los andSHRSP-Aml were significantly reduced compared with SHRSP-Veh but higher thanthat in WKY,there was no difference between SHRSP-Los and SHRSP-Aml.Afterdrug withdrawal,SBP in SHRSP-Los and SHRSP-Aml rised gradually,and SBP inSHRSP-Los rised slower than that in SHRSP-Aml which restored to untreated SHRSPlevel at the age of32weeks, until at the age of40weeks, there were no differenceamong the three groups. Compared with SHRSP-Veh,thinner vascular wall and betterfunction of blood vessel were in SHRSP-Los but not in SHRSP-Aml.The clinicalstroke score in SHRSP-Los was significant lower than that in SHRSP-Veh andSHRSP-Aml (11.00vs23.00and21.17p<0.05); there were edema and blutpunkte onthe surface of brain tissue in SHRsp and SHRSP-Aml but not in SHRSP-Los andWKY;the cerebral cortex presented the chronic hemorrhage stove in SHRSP-Vehand SHRSP-Aml but not in SHRSP-Los and WKY. Compared withSHRSP-Veh,plasma and the cerebral cortex Aldo levels in SHRSP-Los wereremarkedly decreased but plasma AngⅡremarkedly rised,and no significant difference in the cerebral cortex AngⅡ, the cerebral cortex AT1R protein level inSHRSP-Los was down-regulated and AT2R was up-rgulated, whereas no significantdifference was found between SHRSP-Aml and SHRSP-Veh.Conclusion Prehypertensive treatment with losartan was more effective thanamlodipine on delaying blood pressure and ameliorating brain structure and function,also decreasing stroke, which might be achieved by the inhibition of circulating andlocal renin-angiotensin systems.