Arterial baroreflex: a novel target for preventing stroke in rat hypertension.
OBJECTIVE
Arterial baroreflex is one of the most important mechanisms in the regulation of cardiovascular activities. Arterial baroreflex function can be expressed as baroreflex sensitivity (BRS). The present study was designed to test 2 hypotheses: (1) BRS is a new independent predictor for the incidence of stroke in hypertension, and (2) restoration of BRS can prevent stroke in hypertension.


METHODS
First, 82 stroke-prone spontaneously hypertensive rats (SHR-SP) aged 28 to 30 weeks were used. After measuring blood pressure and BRS, the survival time was observed. Second, 12 SHR-SP aged 8 months were used. Blood pressure and BRS were determined separately before and after intragastric administration of ketanserin (0.3 and 3.0 mg/kg). Third, SHR-SP aged 5 months were treated with ketanserin for 12 weeks (0.3 mg and 3.0 mg/kg per day). At the end of the treatment, blood pressure and BRS were determined and the end-organ damage was evaluated. Last, SHR-SP aged 3 months were treated with ketanserin (0.3 and 3.0 mg/kg per day) for life and the survival time was recorded.


RESULTS
Stroke was significantly delayed in rats with high BRS than those with low BRS (time to 50% death was 1.47-fold longer than low BRS group; P<0.01). Ketanserin of 3.0 mg/kg per day decreased blood pressure and enhanced BRS, whereas 0.3 mg/kg per day only enhanced the BRS. Fatal stroke incidences were markedly reduced by treatment with both doses (P<0.0001 versus control group).


CONCLUSIONS
The present study provides evidence that BRS is an independent predictor for stroke in hypertension. Restoration of BRS may be a new strategy for the prevention of stroke.
Liu
Ai-Jun
AJ
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
Ma
Xiu-Juan
XJ
Shen
Fu-Ming
FM
Liu
Jian-Guo
JG
Chen
Hong
H
Su
Ding-Feng
DF
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007650:Ketanserin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000503:physiopathology* / Q000517:prevention & control*
D007650:Ketanserin