Grellet J, Bonoron-Adèle S, Stuyvers B, Tariosse L, Besse P
Department of Physiology and Pharmacology, INSERM U8-Université de Bordeaux II, France.
Cardiovasc Res. 1991 Jun;25(6):484-90. doi: 10.1093/cvr/25.6.484.
The aim was to determine the effects of nicardipine treatment (10-15 mg.kg-1.d-1 intraperitoneal) on left ventricular hypertrophy, coronary haemodynamics, and mechanical performance in renovascular hypertensive rats.
Systemic and coronary haemodynamic variables were evaluated by using microspheres in conscious rats, while mechanical performance and elasticity were measured on isolated papillary muscles from the same animals.
Male Sprague-Dawley rats, weight 150-180 g, were used. Nine treated rats were compared with control groups, consisting of 9 sham operated, 12 untreated hypertensive, and 9 nephrectomised rats.
Eight weeks after clipping, removal of the ischaemic kidney allowed the normalisation of ventricular mass and the reversal of changes induced by hypertrophy except prolongation of timing parameters. Nicardipine administration led to an efficient but incomplete control of blood pressure, which fell from 208(SEM 5) mm Hg in untreated hypertensive rats to 155(4) mm Hg in treated rats, p less than 0.01. After eight weeks of treatment, the reduction in left ventricular mass, from 3.10(0.10) mg.g-1 in untreated rats to 2.72(0.018) mg.g-1 in treated rats was significant (p less than 0.01) but was less than the pressure decrease. In treated hypertensive rats, coronary blood flow was increased and redistributed at rest in favour of the subepicardial layers but was significantly reduced after maximum vasodilatation, to 1.618(0.077) litre.min-1.100 g, in nicardipine treated rats. A reversal of impaired myocardial mechanical indices towards control values was observed except for time to peak force and time to half relaxation.
Nicardipine treatment allowed blood pressure control, reduction of left ventricular mass, and improvement in mechanical performance, but was unable to restore minimal coronary vascular resistance. The results suggest that, although blood pressure decrease is obviously important, it may not be the sole factor in the reversal of cardiac hypertrophy.
本研究旨在确定尼卡地平治疗（腹腔注射，剂量为10 - 15mg·kg⁻¹·d⁻¹）对肾血管性高血压大鼠左心室肥厚、冠状动脉血流动力学及机械性能的影响。
通过微球法评估清醒大鼠的全身及冠状动脉血流动力学变量，同时测量同一动物离体乳头肌的机械性能和弹性。
选用体重150 - 180g的雄性Sprague - Dawley大鼠。将9只接受治疗的大鼠与对照组进行比较，对照组包括9只假手术组、12只未治疗的高血压组和9只肾切除组大鼠。
夹闭肾动脉8周后，切除缺血肾可使心室质量恢复正常，并逆转肥厚引起的变化，但时间参数仍延长。尼卡地平给药可有效但不完全控制血压，未治疗的高血压大鼠血压从208（标准误5）mmHg降至治疗大鼠的155（4）mmHg，p < 0.01。治疗8周后，左心室质量显著降低，从未治疗大鼠的3.10（0.10）mg·g⁻¹降至治疗大鼠的2.72（0.018）mg·g⁻¹（p < 0.01），但低于血压下降幅度。在治疗的高血压大鼠中，静息时冠状动脉血流增加并重新分布，有利于心外膜下层，但在最大血管扩张后显著降低，尼卡地平治疗组大鼠降至1.618（0.077）升·分钟⁻¹·100g。除了达到峰值力的时间和半松弛时间外，观察到受损的心肌机械指标向对照值逆转。
尼卡地平治疗可控制血压、减轻左心室质量并改善机械性能，但无法恢复最小冠状动脉血管阻力。结果表明，虽然血压降低显然很重要，但它可能不是逆转心脏肥厚的唯一因素。
