| Objective To investigate the relationship between central antgiotensin converting enzyme(ACE) and antgiotensin converting enzyme 2(ACE2) and the development of hypertension, the cardiovascular function, the gene expression of and the enzyme activity of ACE and ACE2 in the brain were studied in the prehypertensive rats.Methods Experiments were performed on male spontaneously hypertensive rats(SHR) and normotensive Wistar Kyoto rats(WKY) at 6 and 8 weeks of age. Systolic blood pressure(SBP) and heart rate(HR) were measured by a tail-cuff method. The baroreflex function was assessed by intravenous injection of phenylephrine. Baroreflex sensitivity(BRS) was calculated by the ratio of change in HR to the change in blood pressure before and after phenylephrine administrations. Meanwhile, the gene expression of ACE and ACE2 as well as these enzyme activities were determined in the cardiovascular centers.Results(1) SBP from the SHR was already elevated at 6 weeks of age compared to the age-matched WKY(122.2±7.97 vs 106.6±12.10 mm Hg,P<0.01). Meanwhile, HR of SHR was higher than that of WKY(396.6±19 vs 336±26.3 bpm, P< 0.01). From 6wk to 8wk, SBP in the SHR was increased continuously and reached to 137.8±9.17 mm Hg,which was significantly higher than that of WKY(122±10.62, P< 0.01). Similarly, HR in the SHR was also significantly higher than that of age-matched WKY(376±15 vs 330±18 bpm,P<0.01).(2) Compared to the age-matched WKY, the BRS of 6-wk SHR tend to reduce, but did not reach a significant difference(1.081±0.086 vs 1.14±0.062 bpm/mm Hg). At 8 week of age, however, the BRS of SHR decreased to a greater extent and significantly differed from that of WKY(0.808±0.0.052 vs 1.206±0.226 bpm/mm Hg,P<0.01).(3)Compared to the age-matched WKY, the ACE m RNA expression in the hypothalamic paraventricularnuclus(PVN) was upregulated in the 8-wk SHR(1.000±0.504 vs 1.881±0.213,P<0.05), but ACE2 m RNA expression was significantly downregulated in the PVN of SHR( 1.000±0.343 vs 0.349±0.163,P<0.05).(4) The enzyme activity of ACE in the PVN was increased in the 8-wk SHR compared to the age-matched WKY(38.54±2.93 vs 62.88±8.36 U/min·mg pro,P<0.05),but ACE2 enzyme activity was decreased in PVN of SHR(1.442±0.088 vs 1.749±0.089 μM/min·mg pro,P<0.05).Conlusions In the prehypertensive rats, elevation of blood pressure and heart rate acompanied with the reduced baroreflex function is associated with the upregulation of ACE m RNA and downregulation of ACE2 m RNA in the hypothalamic PVN.Objective The present study was to determeine the effects of exercise training on cardiovascular function and expression of central antgiotensin converting enzyme(ACE) and antgiotensin converting enzyme 2(ACE2) as well as the enzyme activity and to investigate the central mechanism by which exercise training downregulated blood pressure in SHR.Methods Tweenty male 6-wk SHR were assigned randomly into sedentary group(SHR-S, n= 10) and exercise-trained group(SHR-E, n=10). Ten gender- and age-matched Wistar Kyoto rats(WKY) were used as a sedentary contral group(WKY, n=10). The trained rats run on a treadmill in a moderate intensity for 8 weeks. The systolic blood pressure(SBP) and heart rate(HR) were measured biweekly. Twenty-four to forty-egiht hours at the end of exercise training,the baroreflex function, the gene expression of ACE and ACE2 and enzyme activitiy in cardiovascular central system and motor cortex were determined.Results(1) From 6 to 14 weeks of age, the blood pressure in the SHR-S group was elevated from 123.7 ± 7.78 mm Hg to 178.4 ± 8.81 mm Hg. All SHR-S rats developed the high blood pressure(≥140mm Hg) at the end of 8 weeks, which the average of blood pressure was 147.8 ±7.21 mm Hg. During the same period, the blood pressure in the SHR-E group was increased from 120.2 ± 5.65 mm Hg to 165.6±9.37 mm Hg, but the increased value of blood pressure was significantly less in the SHR-E group than in the SHR-S group. Meanwhile the SHR-E rats postponed to develop the hypertension till the end of 10 weeks of age, averaging 149.5±5.48 mm Hg of blood pressue.(2) Compared to the age-matched WKY, the BRS of SHR-S group was decreased(0.627 ± 0.11 vs. 1.292 ± 0.25 bpm/mm Hg; P < 0.01). Exercise training significantly improved the BRS in SHR(1.016 ± 0.123 vs. 0.627± 0.11 Bpm/mm Hg,P < 0.01), but still lower than WKY(1.016±0.123 vs 1.292±0.25 bpm/mm Hg;P<0.01).(3)Compared to the age-matched WKY, the expression of ACE m RNA in RVLM and PVN was already elevated of SHR(P<0.05), and exercise training downregulated the expression(RVLM:0.82±0.37 vs 2.25±0.73,P<0.01;PVN:0.97±0.18 vs 1.99±0.84, P<0.05. Meanwhile, the expression of ACE2 m RNA in PVN was descended of SHR(P<0.05), and exercise training upregulated the expression(2.93±0.7 vs 0.61±0.2,P<0.05)。(4) Compared to the age-matched WKY, the activities of ACE m RN in RVLM and PVN were already elevated of SHR(P<0.05),and exercise training reduced the ACE activities(RVLM:34.45±5.17 vs 68.45±8.66U/min·mg,P<0.05; PVN:24.09±4.42 vs 61±9.11U/min·mg, P<0.01). Meanwhile the activities of ACE2 in PVN was decreased of SHR(P<0.05), and exercise training improved the ACE2 activities(PVN:1.57±0.29 vs 1.04±0.085 μM/min·mg,P<0.05)。Conlusions Exercise training delays the progression from prehypertension to hypertension in SHR and improves cardiovascular function, which is associated with the improvement of gene expression and enzyme activity of ACE2 as well as reduction in ACE gene expression and enzyme activity in the cardiovascular centers. |
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