高血圧自然発症ラットにおけるβ遮断薬と運動の併用効果

Abstract

We investigated the effects of long-term administration of bisoprolol (β-blocker), exercise and their combination on blood pressure, heart rate, and baroreflex function in spontaneously hypertensive rats (SHR).SHR aged 5 week were randomly assigned to control group (C), bisoprolol-treated group (Biso), exercise group (Exer), and combination group (Biso+Exer)(n=8/each group). In Biso and Biso+Exer, bisoprolol (20 mg/kg/day) was administered. In Exer and Biso+Exer, exercise training was performed on treadmill 5 days/week for 12 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured using the tail-cuff method under restraint from 5 to 16 weeks of age. After 12-week intervention period, sigmoidal mean artery pressure (MAP) and HR reflex curve were obtained by intravenous injections of various doses of phenylephrine and nitroprusside under non-restraint condition. To determine vagal component of baroreflex function, baroreflex MAP-HR relation were also examined after intravenous injections of atenolol (β-blocker). After measurements of all baroreflex function, atropine was additionally injected to determine intrinsic HR.At 15 and 16 weeks of age, SBP and HR in Biso and Exer were significantly lower than those in C. SBP and HR in Biso+Exer were further reduced compared with Biso. Before atenolol, resting MAP, HR and upper and lower HR plateaus in the sigmoid curve were lower in Biso, Exer, and Biso+Exer compared with C. There were no significant differences in these parameters between Biso and Biso+Exer. There were no significant differences in baroreflex gain before atenolol among the four groups except for between Biso and Biso+Exer. After atenolol, baroreflex gain and HR range in Biso, Exer, and Biso+Exer were significantly higher than those in C. HR range of sympathetic component (upper HR plateau before atenolol-itrinsic HR) was significantly reduced in Biso, Exer, and Biso+Exer compared with C. There were no significant differences in baroreflex gain of vagal component or HR range of vagal and sympathetic component between Biso and Biso+Exer.These findings suggest that both chronic treatment with β-blocker and exercise decrease resting blood pressure and HR in SHR, associated with reduced sympathetic component and increased vagal component of baroreflex function. The additive effects of β-blocker and exercise are not evident under non-stressful conditions, but could be obtained in the presence of stress such as restraint.