Nishimura H, Kubota J, Okabe M, Ueyama M, Kawamura K
Third Department of Internal Medicine, Osaka Medical College, Japan.
Jpn Circ J. 1992 Mar;56(3):255-61. doi: 10.1253/jcj.56.255.
This study investigated whether nifedipine administered in divided daily doses would diminish left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). We administered nifedipine (12 mg/kg/day) in 3 divided doses by gastric gavage to 15-week-old male SHR (n = 10) for 4 weeks. Age- and sex-matched SHR served as controls (n = 10). Left ventricular (LV) function was evaluated by LV catheterization and cardiac output was determined by the thermodilution method. Plasma renin activity (PRA) and plasma norepinephrine levels were measured. Nifedipine significantly decreased blood pressure (p less than 0.01), shortened time constant T (p less than 0.05), and increased cardiac output (p less than 0.05). Nifedipine did not impair the LV systolic and diastolic indices during acute afterload elevation with angiotensin II. LV weight was similar in the 2 groups of rats. While PRA was unaltered, plasma norepinephrine levels were higher in the nifedipine-treated rats (p less than 0.05). These data indicate that nifedipine in 3 divided doses reduced blood pressure in SHR without compromising cardiac function but did not reverse LVH. The short hypotensive duration of nifedipine and its enhancement of sympathetic nervous activity may be responsible for the failure to reverse LVH, despite adequate blood pressure control.
本研究调查了每日分剂量给予硝苯地平是否会减轻自发性高血压大鼠（SHR）的左心室肥厚（LVH）。我们通过胃管以3次分剂量给予15周龄雄性SHR（n = 10）硝苯地平（12 mg/kg/天），持续4周。年龄和性别匹配的SHR作为对照（n = 10）。通过左心室插管评估左心室（LV）功能，并通过热稀释法测定心输出量。测量血浆肾素活性（PRA）和血浆去甲肾上腺素水平。硝苯地平显著降低血压（p < 0.01），缩短时间常数T（p < 0.05），并增加心输出量（p < 0.05）。在使用血管紧张素II急性增加后负荷期间，硝苯地平不损害左心室收缩和舒张指标。两组大鼠的左心室重量相似。虽然PRA未改变，但硝苯地平治疗组大鼠的血浆去甲肾上腺素水平较高（p < 0.05）。这些数据表明，分3次剂量给予的硝苯地平可降低SHR的血压而不损害心脏功能，但不能逆转LVH。尽管血压得到充分控制，但硝苯地平较短的降压持续时间及其对交感神经活动的增强可能是未能逆转LVH的原因。
