Hansen J M, Fogh-Andersen N, Christensen N J, Strandgaard S
Department of Clinical Physiology, Herlev Hospital, University of Copenhagen, Denmark.
J Hypertens. 1997 Mar;15(3):319-26. doi: 10.1097/00004872-199715030-00014.
To investigate the effect of cyclosporine A (CsA; Sandimmun Neoral) on systemic and renal hemodynamics, tubular function, and sodium excretion in healthy volunteers. Furthermore, we studied whether CsA enhances the systemic and renal hemodynamic sensitivity to norepinephrine.
Eighteen healthy volunteers were administered 10 mg/kg CsA or placebo capsules in a double-blind fashion. The mean arterial blood pressure (MAP), renal vascular resistance (RVR), glomerular filtration rate (GFR), and renal clearances of lithium (CLi) and sodium (CNa) were measured for 8 h after ingestion of the capsules. Norepinephrine (2 microg/kg per h) was infused intravenously for 1.5 h into nine subjects.
CsA increased the MAP by 17+/-2 mmHg. The GFR decreased by 18+/-2% (P < 0.001) and the RVR increased by 37+/-4% (P< 0.001) after ingestion of CsA. The CsA-induced increase in MAP preceded the CsA-induced fall in GFR. The rise in MAP was followed by an early 35+/-8/0 increase in CNa (P < 0.001). At the end of the 8 h study period, CNa decreased by 25+/-7% (P < 0.001). Using CLi, it was found that the initial natriuresis had been caused by a relative decrease both in proximal and in distal tubular reabsorption of sodium, whereas the late sodium retention was secondary to the CsA-induced fall in GFR. Infusion of norepinephrine increased the MAP, RVR, and filtration fraction, and decreased the renal plasma flow, without CsA having any additional effect.
It was demonstrated that a single oral dose of CsA caused a rise in blood pressure and transient natriuresis, followed by a fall in GFR and antinatriuresis. Thus, the present study confirms and extends earlier observations that renal dysfunction and sodium retention are not the initiating events in CsA-induced hypertension. The study also affords evidence suggesting that such rises in blood pressure are not mediated by an increased sensitivity to norepinephrine.
研究环孢素A（CsA；新山地明）对健康志愿者全身及肾脏血流动力学、肾小管功能和钠排泄的影响。此外，我们还研究了CsA是否增强了对去甲肾上腺素的全身及肾脏血流动力学敏感性。
18名健康志愿者以双盲方式服用10mg/kg CsA或安慰剂胶囊。在服用胶囊后8小时内测量平均动脉血压（MAP）、肾血管阻力（RVR）、肾小球滤过率（GFR）以及锂（CLi）和钠（CNa）的肾脏清除率。对9名受试者静脉输注去甲肾上腺素（每小时2μg/kg），持续1.5小时。
CsA使MAP升高17±2mmHg。服用CsA后，GFR下降18±2%（P<0.001），RVR升高37±4%（P<0.001）。CsA引起的MAP升高先于CsA引起的GFR下降。MAP升高后，CNa早期升高35±8%（P<0.001）。在8小时研究期结束时，CNa下降25±7%（P<0.001）。利用CLi发现，最初的利钠是由于近端和远端肾小管对钠的重吸收相对减少所致，而后期的钠潴留是CsA引起的GFR下降的继发结果。输注去甲肾上腺素使MAP、RVR和滤过分数升高，肾血浆流量下降，而CsA无任何额外影响。
结果表明，单次口服CsA可导致血压升高和短暂利钠，随后GFR下降和钠潴留。因此，本研究证实并扩展了早期的观察结果，即肾功能障碍和钠潴留不是CsA诱导的高血压的起始事件。该研究还提供了证据表明，这种血压升高不是由对去甲肾上腺素敏感性增加介导的。
