Huysmans F T, van Hamersvelt H W, Sluiter H E, Wetzels J F, Koene R A
Department of Medicine, Sint Radboud Hospital, University of Nijmegen, The Netherlands.
Kidney Int Suppl. 1992 May;36:S106-9.
In contrast to other types of directly acting vasodilators, calcium antagonists promote sodium excretion. It is not well established, however, whether these drugs also induce natriuresis in hypertensive patients with renal disease. Therefore, we studied the acute effects of the dihydropyridine calcium antagonist felodipine in nine such patients (CCr 68 +/- 19 ml/min) and 12 healthy normotensive subjects. In both the hypertensive patients and the normotensive subjects total and fractional sodium excretion rose during the first 40 minutes of intravenous felodipine infusion; in the hypertensive patients this rise of sodium excretion was positively correlated to the initial glomerular filtration rate (GFR) (r = 0.87, P less than 0.01). In the patients, during ongoing felodipine infusion, natriuresis was attenuated in the setting of a large continuing decrease of blood pressure. In contrast, in the normotensive subjects, in whom blood pressure did not fall any further, a steady rise of sodium excretion was observed. In both the hypertensive patients and the normotensive subjects GFR remained unchanged and renal vascular resistance decreased, whereas renal plasma flow increased only in the latter group. Changes in sodium excretion were not correlated to changes in renal hemodynamic parameters. It is concluded, that also in hypertensive patients with diminished renal function felodipine exerts a potentially advantageous natriuretic effect. However, this natriuretic effect is possibly less at lower GFR and seems to be attenuated by blood pressure reduction. The mechanism of this natriuretic effect as well as its contribution to the antihypertensive effect of felodipine still has to be clarified.
与其他类型的直接作用血管扩张剂不同，钙拮抗剂可促进钠排泄。然而，这些药物是否也能在患有肾脏疾病的高血压患者中诱导利钠作用，目前尚未明确。因此，我们研究了二氢吡啶类钙拮抗剂非洛地平对9例此类患者（肌酐清除率68±19 ml/min）和12例健康血压正常受试者的急性作用。在高血压患者和血压正常受试者中，静脉输注非洛地平的前40分钟内，总钠排泄量和钠排泄分数均升高；在高血压患者中，钠排泄量的这种升高与初始肾小球滤过率（GFR）呈正相关（r = 0.87，P < 0.01）。在患者中，持续输注非洛地平期间，在血压持续大幅下降的情况下，利钠作用减弱。相比之下，在血压不再下降的血压正常受试者中，观察到钠排泄量持续升高。在高血压患者和血压正常受试者中，GFR均保持不变，肾血管阻力降低，而仅在后一组中肾血浆流量增加。钠排泄的变化与肾血流动力学参数的变化无关。得出的结论是，即使在肾功能减退的高血压患者中，非洛地平也具有潜在的有利利钠作用。然而，在较低的GFR时，这种利钠作用可能较小，并且似乎会因血压降低而减弱。这种利钠作用的机制及其对非洛地平降压作用的贡献仍有待阐明。
