Head G A, Minami N
Baker Medical Research Institute, Prahran, Victoria, Australia.
Am J Med. 1992 Apr 27;92(4B):54S-59S. doi: 10.1016/0002-9343(92)90148-5.
In the present study, we examined whether antihypertensive treatment of young and adult hypertensive rats with the angiotensin-converting enzyme (ACE) inhibitor perindopril could restore the baroreflex vagal deficit and whether this was related to prevention of cardiac or vascular hypertrophy. Spontaneously hypertensive (SHR), stroke-prone spontaneously hypertensive (SHR-SP), and Wistar-Kyoto (WKY) rats were untreated or treated with perindopril (3 mg/kg/day) in the drinking water from 4-9 and from 14-20 weeks of age. Steady-state sigmoidal mean arterial pressure (MAP)-heart rate (HR) reflex curves were obtained in the conscious rats by the injection of pressor and depressor agents before and after atenolol (vagal component). Increased left ventricle to bodyweight ratio (LV/BW) indicated cardiac hypertrophy. After ganglion blockade, the minimum MAP produced by nitroprusside and the maximum produced by methoxamine were used as indications of vascular hypertrophy. Perindopril treatment reduced cardiac and vascular hypertrophy to different extents in SHR and SHR-SP. The 4-9 and 14-20 week treatments reduced MAP and both minimum and maximum blood pressure of the SHR to the levels of the untreated WKY. However, only in the older animals was LV/BW restored. In the SHR-SP, early treatment had a much greater effect on vascular hypertrophy than on LV/BW. The reverse occurred for the 14-20 week animals. In untreated hypertensive animals the baroreflex curves were shifted to the right with reduced vagal HR range. Perindopril treatment shifted the baroreflex curves back towards the WKY curves. Vagal HR range was strongly correlated with the LV/BW, whereas vagal HR range was less well related to the level of vascular hypertrophy or blood pressure. These results suggest that antihypertensive treatment can restore cardiac baroreflex function and that it is related to the reduction in cardiac hypertrophy. Although the mechanism of this relationship remains to be elucidated, these findings suggest that cardiac vagal afferents may be important.
在本研究中，我们检测了用血管紧张素转换酶（ACE）抑制剂培哚普利对年轻和成年高血压大鼠进行抗高血压治疗是否能恢复压力反射性迷走神经功能缺陷，以及这是否与预防心脏或血管肥大有关。自发性高血压（SHR）大鼠、易卒中型自发性高血压（SHR-SP）大鼠和Wistar-Kyoto（WKY）大鼠未接受治疗，或在4至9周龄以及14至20周龄时通过饮用水给予培哚普利（3毫克/千克/天）治疗。在有意识的大鼠中，通过注射升压药和降压药，在给予阿替洛尔（迷走神经成分）前后获得稳态S形平均动脉压（MAP）-心率（HR）反射曲线。左心室与体重比（LV/BW）增加表明存在心脏肥大。在神经节阻断后，硝普钠产生的最低MAP和甲氧明产生的最高MAP被用作血管肥大的指标。培哚普利治疗在不同程度上减轻了SHR和SHR-SP大鼠的心脏和血管肥大。4至9周和14至20周的治疗将SHR的MAP以及最低和最高血压降至未治疗WKY大鼠的水平。然而，只有在年龄较大的动物中，LV/BW才恢复正常。在SHR-SP大鼠中，早期治疗对血管肥大的影响比对LV/BW的影响大得多。对于14至20周龄的动物，情况则相反。在未治疗的高血压动物中，压力反射曲线向右移位，迷走神经HR范围减小。培哚普利治疗使压力反射曲线向WKY大鼠的曲线方向回移。迷走神经HR范围与LV/BW密切相关，而迷走神经HR范围与血管肥大程度或血压的相关性则较弱。这些结果表明，抗高血压治疗可以恢复心脏压力反射功能，并且这与心脏肥大的减轻有关。尽管这种关系的机制仍有待阐明，但这些发现表明心脏迷走神经传入可能很重要。
