Niederberger M, Aubert J F, Nussberger J, Brunner H R, Waeber B
Division of Hypertension, University Hospital, Lausanne, Switzerland.
J Hypertens. 1995 Apr;13(4):439-45.
To assess in conscious two-kidney, one clip renal hypertensive rats whether angiotensin converting enzyme (ACE) inhibition with lisinopril, angiotensin II receptor blockade with losartan or vasodilation with sodium nitroprusside have similar effects on intra-arterial mean blood pressure, heart rate and splanchnic nerve activity.
A bolus dose of lisinopril or losartan (both 10 mg/kg, intravenously) induced within 2 h an equal reduction in mean blood pressure, whereas sodium nitroprusside infused during the same period (at 10 micrograms/min) lowered mean blood pressure, but less strongly. The heart rate was accelerated significantly more during sodium nitroprusside infusion than during lisinopril or losartan treatment. Splanchnic nerve activity increased significantly only in those rats given sodium nitroprusside. No change in the parameters studied was observed in vehicle-treated rats. The doses of lisinopril and losartan were repeated after 12 and 24 h. Before administration of the last dose, the mean blood pressure was still low. Administration of lisinopril or losartan again 24 h after the initial dose had no further effect on the mean blood pressure, heart rate or splanchnic nerve activity.
These results obtained in rats with a renin-dependent form of hypertension show that blockade of the renin-angiotensin system for 24 h produces an equivalent blood pressure reduction irrespective of whether it is due to ACE inhibition or angiotensin II antagonism. The results also indicate that there is less reflex activation of sympathetic nerve activity when blood pressure is lowered with a blocker of the renin-angiotensin system rather than with a direct vasodilator such as sodium nitroprusside.
评估清醒状态下的两肾一夹肾性高血压大鼠,赖诺普利抑制血管紧张素转换酶(ACE)、氯沙坦阻断血管紧张素II受体或硝普钠舒张血管对动脉平均血压、心率和内脏神经活动是否有相似的作用。
静脉注射大剂量赖诺普利或氯沙坦(均为10mg/kg)在2小时内使平均血压同等程度降低,而同期输注硝普钠(10微克/分钟)使平均血压降低,但降低幅度较小。输注硝普钠期间心率的加速显著大于赖诺普利或氯沙坦治疗期间。仅在给予硝普钠的大鼠中内脏神经活动显著增加。在给予赋形剂的大鼠中未观察到所研究参数的变化。12小时和24小时后重复给予赖诺普利和氯沙坦的剂量。在给予最后一剂之前,平均血压仍然较低。初始剂量24小时后再次给予赖诺普利或氯沙坦对平均血压、心率或内脏神经活动没有进一步影响。
在肾素依赖性高血压大鼠中获得的这些结果表明,阻断肾素-血管紧张素系统24小时可产生同等程度的血压降低,无论其是由于ACE抑制还是血管紧张素II拮抗。结果还表明,与使用直接血管舒张剂如硝普钠降低血压相比,使用肾素-血管紧张素系统阻滞剂降低血压时交感神经活动的反射性激活较少。