Ketanserin-induced baroreflex enhancement in spontaneously hypertensive rats depends on central 5-HT(2A) receptors

Abstract

1. Ketanserin may influence baroreflex function by blocking 5-HT(2A) receptors and/or alpha(1)-adrenoceptors through central and/or peripheral mechanisms. 2. In the present study, we tested the hypothesis that the baroreflex sensitivity (BRS)-enhancing effects of ketanserin are mediated by central 5-HT(2A) receptors in spontaneously hypertensive rats (SHR). 3. Using a conjugate of a monoclonal antibody to the serotonin reuptake transporter (SERT) and the toxin saporin (anti-SERT-SAP), which specifically eliminates the neurons that express SERT, the effects of ketanserin (0.3 and 3.0 mg/kg, i.g.) on BRS, blood pressure (BP), heart period (HP) and blood pressure variability (BPV) were compared between conscious intact SHR and SHR pretreated with anti-SERT-SAP. 4. Immunochemistry showed that, 2 weeks after intracerebroventricular injection of the toxin, 5-HT expression was strikingly attenuated in the brain, whereas values of BRS, BPV and BP were similar to those in the sham group. In intact SHR, 0.3 mg/kg ketanserin significantly improved BRS (191% control) and reduced BPV without affecting BP; at 3.0 mg/kg, ketanserin significantly increased BRS (197% control) and decreased BPV and BP. In toxin-pretreated SHR, only the high dose of ketanserin improved BRS (132% control), neither of the ketanserin doses reduced BPV, but both significantly decreased BP. 5. We conclude that the BRS-enhancing effects of ketanserin are mediated largely by central 5-HT(2A) receptors, whereas the antihypertensive effect of ketanserin persists even after destruction of serotonergic neurons in the central nervous system.