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KETANSERIN‐INDUCED BAROREFLEX ENHANCEMENT IN SPONTANEOUSLY HYPERTENSIVE RATS DEPENDS ON CENTRAL 5‐HT 2A RECEPTORS
Author(s) -
Shen FuMing,
Wang Jin,
Ni CanRong,
Yu JianGuang,
Wang WeiZhong,
Su DingFeng
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04626.x
Subject(s) - ketanserin , baroreflex , endocrinology , medicine , receptor , chemistry , serotonin , 5 ht receptor , serotonergic , blood pressure , pharmacology , heart rate
SUMMARY1 Ketanserin may influence baroreflex function by blocking 5‐HT 2A receptors and/or α 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.