Magri P, Rao M A, Cangianiello S, Bellizzi V, Russo R, Mele A F, Andreucci M, Memoli B, De Nicola L, Volpe M
Cattedra di Nefrologia and I Clinica Medica-Università di Napoli Federico II, Italy.
Circulation. 1998;98(25):2849-54. doi: 10.1161/01.cir.98.25.2849.
The early/asymptomatic stages of heart failure (HF) are characterized by sodium retention secondary to derangement of sodium reabsorption at the proximal nephron level. Because this phenomenon is reversed by ACE inhibition, abnormalities of renal sodium handling may depend on intrarenal changes of angiotensin II (AII)/nitric oxide (NO) levels. Renal hemodynamic reserve (ie, the glomerular vasodilatory response to amino acid infusion) has been proposed as a reliable test to assess in vivo AII/NO balance.
In this study, the effects of 6 weeks of treatment with 5 mg/d of enalapril or with 50 mg/d of losartan on systemic hemodynamics and renal function were assessed, at baseline and after amino acid infusion (AA), in patients with mild HF (NYHA class I) and in healthy volunteers. Untreated HF patients showed a basal renal function comparable to that of healthy subjects. After AA, glomerular filtration rate and renal plasma flow significantly increased in healthy subjects (+29.0% and +30.4%, respectively), whereas no vasodilatory response was observed in HF. Although they did not affect basal renal hemodynamics, both enalapril and losartan restored a normal response to AA in HF patients. Blood pressure and heart rate were comparable in HF subjects and healthy subjects at baseline and were not modified by either treatment. Left ventricular ejection fraction was depressed in HF but did not change after either drug. Urinary excretions of cGMP and nitrate (indexes of NO activity in the kidney), comparable in healthy subjects and in HF patients, were unchanged by either enalapril or losartan and did not correlate with renal reserve.
(1) Renal functional reserve is absent in patients with early/asymptomatic HF and normal renal function and (2) both enalapril and losartan restore a normal vasodilatory response to AA in these patients without affecting basal systemic and renal hemodynamics. These data suggest a major role of AII in the development of early abnormalities in patients with HF.
心力衰竭（HF）的早期/无症状阶段的特征是由于近端肾单位水平钠重吸收紊乱继发钠潴留。由于这种现象可被血管紧张素转换酶（ACE）抑制所逆转，肾脏钠处理异常可能取决于肾内血管紧张素II（AII）/一氧化氮（NO）水平的变化。肾血流动力学储备（即肾小球对氨基酸输注的血管舒张反应）已被提议作为评估体内AII/NO平衡的可靠试验。
在本研究中，评估了5mg/d依那普利或50mg/d氯沙坦治疗6周对轻度HF（纽约心脏协会I级）患者和健康志愿者在基线和氨基酸输注（AA）后全身血流动力学和肾功能的影响。未经治疗的HF患者的基础肾功能与健康受试者相当。AA后，健康受试者的肾小球滤过率和肾血浆流量显著增加（分别增加29.0%和30.4%），而HF患者未观察到血管舒张反应。尽管依那普利和氯沙坦均未影响基础肾血流动力学，但二者均使HF患者对AA恢复了正常反应。HF受试者和健康受试者在基线时的血压和心率相当，且两种治疗均未使其改变。HF患者的左心室射血分数降低，但两种药物治疗后均未改变。健康受试者和HF患者中相当的尿中环鸟苷酸（cGMP）和硝酸盐（肾脏中NO活性指标）排泄量，未被依那普利或氯沙坦改变，且与肾储备无关。
（1）早期/无症状HF且肾功能正常的患者不存在肾功能储备；（2）依那普利和氯沙坦均可使这些患者对AA恢复正常的血管舒张反应，而不影响基础全身和肾血流动力学。这些数据表明AII在HF患者早期异常的发生中起主要作用。
