title: Effects of low-dose ketanserin on atherosclerosis in rats and rabbits.
abstract: The present study was designed to test the hypothesis that a small dose of ketanserin, which enhances baroreflex activity, prevents the early lesions of atherosclerosis. In experiment 1, baroreflex sensitivity (BRS) was measured in 31 spontaneously hypertensive rats (SHRs) in a conscious state using a computerized blood pressure monitoring system. Four weeks later, the rats were administered vitamin D3 and fed a high-cholesterol diet for 8 weeks to induce atherosclerosis. Then their hearts and aortae were removed for pathological examination. A negative correlation was found between BRS and the scores of coronary (r = -0.460, P < 0.01) and aortic atherosclerosis (r = -0.448, P < 0.05) in SHR. In experiment 2, SHRs were divided into 3 groups (n = 10 in each group) and received a dose of ketanserin of 0.3, 1.0, and 3.0 mg/kg (i.g.), respectively. At the smallest dose (0.3 mg/kg), ketanserin did not lower blood pressure but enhanced BRS. In experiment 3, SHRs were administered vitamin D3, fed a high-cholesterol diet, and simultaneously treated with low-dose ketanserin. The atherosclerosis scores of the treatment group were significantly lower than those of the control group (coronary score: 0.90 ± 0.14 vs. 1.76 ± 0.27, P < 0.05; aortic scores: 1.00 ± 0.39 vs. 2.18 ± 0.41, P < 0.05). In experiment 4, male New Zealand White rabbits were fed a high-cholesterol diet and treated with low-dose ketanserin at the same time. The atherosclerosis scores of the treatment group were significantly lower than those of the control group (aortic scores: 0.26 ± 0.20 vs. 0.60 ± 0.31, P < 0.05). In conclusion, the present study demonstrated, for the first time, that low-dose ketanserin prevented the development of atherosclerosis independent of its blood pressure lowering action in SHRs and New Zealand White rabbits at least in part via enhancement of arterial baroreflex function.
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Yu
authors.forename: He-Hui
authors.initials: HH
authors.lastname: Xie
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Song
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Cai
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000503:physiopathology / Q000517:prevention & control*; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D007650:Ketanserin / Q000627:therapeutic use*; D008297:Male; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D012702:Serotonin Antagonists / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D012702:Serotonin Antagonists; D007650:Ketanserin