Effect Of Ketanserin On Arterial Baroreflex In Rats And Its Mechanism

Science the end of the 1980's, the pathological importance of baroreflex function has attracted the attention of many investigators. In our previous studies, it was found that ketanserin (ket) lowered blood pressure (BP), decreased BP variability (BPV) and enhanced baroreflex sensitivity (BRS). The present work was designed to test the hypothesis that the reatoration of BRS by ket is not dependent on BP level in conscious rats.Spontaneously hypertension rats (SHR) aged 8-12months were used. BP was recoded for 60 min and BRS was determined separately before and after intragastric administration of ket, with four doses( 0.3, 1.0, 3.0, 10.0 mg/kg). Ket significantly decreased systolic BPV(SBPV) and diastolic BPV (DBPV) in non-dose-dependent way. BRS was restored in all four doses groups of rats. And the decrease of BPV and restoration of BRS were not dependent on the BP level. 10- week-old SD rats were used for preparing a myocardial infaction (MI) model by ligating the coronary artery. BRS was destroyed in MI rats. Ket (10, 0.6 mg/kg/d, for 4-5 weeks) significantly restored BRS of MI rats to sham operated rats. Ket had no effects on BP and BRS in SD rats.Ket was mixed in rat chow at dose of 0.1 mg/kg/d. SHR were treated for 4 months. It was found that long-term treatment with low-dose ket did not lower BP level, but significantly decreased BPV, enhanced BRS and reduced organ damage in SHR. Multiple-regression analysis showed that decrease in left ventricular hypertrophy was mainly determined by increase in BRS, decrease in aortic hypertrophy was predicted by decrease in diastolic BPV, and amelioration in renal lesion was mainly determined by increase in BRS and decrease in diastolic BPV.Prazosin (0.5mg/kg) and retanserin (0.625mg/kg) did not effect BRS in SHR when given by i.v.. However, when given i.c.v., prazosin slightly enhanced BRS (p<0.05)and ritanserin markedly enhanced BRS (p<0.001) in SHR. The results indicated ket restoration of BRS is mediated by central 5-HT_2A The following experiments were designed to investigate the mechanism of action of...