Higashi Y, Oshima T, Ozono R, Matsuura H, Kambe M, Kajiyama G
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Am J Hypertens. 1999 Jan;12(1 Pt 1):8-15. doi: 10.1016/s0895-7061(98)00204-0.
This study was designed to compare the renal endothelial function in patients with essential hypertension and normal renal function with that in hypertensive patients with renal insufficiency. We studied the effects of L-arginine (500 mg/kg intravenously over 30 min) on renal hemodynamics in 30 normotensive control subjects, 32 patients with mild to moderate essential hypertension who had normal renal function, and seven hypertensive patients with renal insufficiency who had a serum creatinine concentration >2.0 mg/mL and a glomerular filtration rate <50 mL/min/1.48 m2. L-Arginine infusion similarly reduced the mean blood pressure between the three groups (normotensive: -9.7% +/- 0.7%, hypertensives with normal renal function: -10.2% +/- 0.8%, and hypertensives with renal insufficiency: -8.2% +/- 1.3%). The L-arginine-induced decrease in renal vascular resistance was smaller in essential hypertensive patients than in normotensive subjects (-11.0% +/- 2.2 v -19.8% +/- 2.1%, P <.05). However, L-arginine had no effect on the renal vascular resistance in hypertensive patients with renal insufficiency (1.6% +/- 4.8%). Urine nitrite/nitrate levels in response to L-arginine significantly increased in the three groups in the following order: patients with renal insufficiency (47% +/- 15%), essential hypertensive patients (87% +/- 10%), and normotensive subjects (129% +/- 12%). The glomerular filtration rate was unaffected by L-arginine in normotensive and essential hypertensive patients (3.1% +/- 2.4% and 4.2% +/- 2.5%), but significantly decreased in hypertensive patients with renal insufficiency (-13.7% +/- 6.1%). These findings suggest that the ability of the L-arginine-nitric oxide-cGMP pathway to relax the renal vascular tone may be impaired in essential hypertensive patients and more markedly blunted in hypertensive patients with renal insufficiency, in parallel with increasing serum creatinine concentrations.
本研究旨在比较肾功能正常的原发性高血压患者与肾功能不全的高血压患者的肾内皮功能。我们研究了L-精氨酸(500mg/kg静脉注射,30分钟内)对30名血压正常的对照受试者、32名肾功能正常的轻度至中度原发性高血压患者以及7名血清肌酐浓度>2.0mg/mL且肾小球滤过率<50mL/min/1.48m²的肾功能不全高血压患者肾血流动力学的影响。三组患者静脉输注L-精氨酸后平均血压均有相似程度的降低(血压正常者:-9.7%±0.7%,肾功能正常的高血压患者:-10.2%±0.8%,肾功能不全的高血压患者:-8.2%±1.3%)。原发性高血压患者中L-精氨酸诱导的肾血管阻力降低幅度小于血压正常者(-11.0%±2.2%对-19.8%±2.1%,P<.05)。然而,L-精氨酸对肾功能不全的高血压患者的肾血管阻力无影响(1.6%±4.8%)。三组患者中,L-精氨酸刺激后的尿亚硝酸盐/硝酸盐水平按以下顺序显著升高:肾功能不全患者(47%±15%)、原发性高血压患者(87%±10%)、血压正常者(129%±12%)。L-精氨酸对血压正常和原发性高血压患者的肾小球滤过率无影响(分别为3.1%±2.4%和4.2%±2.5%),但在肾功能不全的高血压患者中显著降低(-13.7%±6.1%)。这些发现表明,原发性高血压患者中L-精氨酸-一氧化氮-cGMP途径舒张肾血管张力的能力可能受损,而在肾功能不全的高血压患者中更明显地减弱,且与血清肌酐浓度升高平行。