Hoogenberg K, Navis G, Dullaart R P
Department of Internal Medicine, Groningen State University Hospital, The Netherlands.
Nephrol Dial Transplant. 1998 Mar;13(3):640-5. doi: 10.1093/ndt/13.3.640.
In non-diabetic subjects, an attenuated systemic norepinephrine (NE) responsiveness may contribute to the mechanisms of action of angiotensin-converting enzyme (ACE) inhibitor treatment. We determined whether ACE inhibitor treatment influences systemic and renal haemodynamic responsiveness to exogenous NE, as well as urinary albumin excretion during NE, in microalbuminuric insulin-dependent diabetic (IDDM) patients, representing a patient category that benefits by strict blood pressure control.
In seven microalbuminuric IDDM patients, systemic and renal responsiveness to NE, infused at individually determined threshold [deltamean arterial pressure (MAP)=0 mmHg], 20% pressor (deltaMAP=4 mmHg) and pressor (deltaMAP=20 mmHg) doses, were compared before and after 8 weeks treatment with enalapril, 10 mg daily. Blood glucose was clamped at 5 mmol/l and insulin was infused at 30 mU/kg/h.
Enalapril decreased MAP (P<0.05) and microalbuminuria (P<0.05), whereas effective renal plasma flow (ERPF) increased (P<0.01) and glomerular filtration rate remained unaltered. The filtration fraction tended to decline (P=0.09). The ACE inhibitor-induced fall in MAP disappeared at NE pressor dose, and the overall mean increase in MAP in response to NE was even higher with than without enalapril (P<0.05). After enalapril, the ERPF remained higher at all NE doses (P<0.05), but the magnitude of the NE-induced fall in ERPF was not altered by ACE inhibition treatment. Overnight urinary albumin excretion fell with ACE inhibition (P<0.05), but this effect was not seen during NE infusion. The angiotensin II/active renin ratio and serum aldosterone levels remained lower with enalapril at all NE doses (P<0.05).
Enalapril does not attenuate systemic and renal vascular responsiveness to exogenous NE in microalbuminuric IDDM despite adequate inhibition of the renin-angiotensin-aldosterone system. These findings suggest that the effect of NE on vasoconstriction is not counteracted effectively by ACE inhibition treatment alone.
在非糖尿病患者中，全身性去甲肾上腺素（NE）反应性减弱可能参与了血管紧张素转换酶（ACE）抑制剂的作用机制。我们确定了ACE抑制剂治疗是否会影响微量白蛋白尿的胰岛素依赖型糖尿病（IDDM）患者对外源性NE的全身和肾脏血流动力学反应，以及NE输注期间的尿白蛋白排泄，这类患者通过严格控制血压可从中获益。
在7例微量白蛋白尿的IDDM患者中，比较了每日服用10 mg依那普利治疗8周前后，对分别确定的阈值[平均动脉压（MAP）变化=0 mmHg]、升压20%（MAP变化=4 mmHg）和升压（MAP变化=20 mmHg）剂量的NE的全身和肾脏反应。血糖维持在5 mmol/L，胰岛素以30 mU/kg/h的速度输注。
依那普利使MAP降低（P<0.05），微量白蛋白尿减少（P<0.05），而有效肾血浆流量（ERPF）增加（P<0.01），肾小球滤过率保持不变。滤过分数有下降趋势（P=0.09）。在NE升压剂量下，ACE抑制剂引起的MAP下降消失，与未使用依那普利相比，NE引起的MAP总体平均升高甚至更高（P<0.05）。使用依那普利后，在所有NE剂量下ERPF均保持较高水平（P<0.05），但ACE抑制治疗并未改变NE引起的ERPF下降幅度。夜间尿白蛋白排泄在ACE抑制时减少（P<0.05），但在NE输注期间未观察到这种效应。在所有NE剂量下，依那普利治疗后血管紧张素II/活性肾素比值和血清醛固酮水平均保持较低（P<0.05）。
尽管依那普利充分抑制了肾素-血管紧张素-醛固酮系统，但在微量白蛋白尿的IDDM患者中，它并未减弱对外源性NE的全身和肾血管反应。这些发现表明，单独的ACE抑制治疗不能有效抵消NE对血管收缩的作用。
