Roccatello D, Mosso R, Ferro M, Polloni R, De Filippi P G, Quattrocchio G, Bancale E, Cesano G, Sena L M, Piccoli G
Istituto di Nefro-Urologia, Università di Torino, Italy.
Clin Nephrol. 1994 Jun;41(6):323-30.
The vasoconstrictor peptide endothelin-1 (ET1) has only recently been characterized and its effects are at present largely speculative. It has been hypothesized that ET1 acts on mesangial cells to cause vasoactive changes which might ultimately contribute to the development of glomerulosclerosis. Opposite to ET1, nitric oxide (NO) inhibits mesangial cell contraction and proliferation. NO activates soluble guanylic acid cyclase and the final product, cyclic GMP (cGMP), has been recently used as a marker of NO action. Urinary levels of ET1 and cGMP were detected in 58 patients with biopsy-proven glomerulonephritis (GN), including 36 IgA nephropathy (IgAGN), 30 with normal and 6 with impaired renal function, 10 patients with non-IgA mesangial GN and 12 pts with membranous GN (MGN) with normal renal function. Compared to normal controls (0.019 +/- 0.006 ng/min), urine ET1 levels were significantly higher in patients with normal renal function having IgAGN (0.035 +/- 0.017, p < 0.01), MGN (0.028 +/- 0.013, p < 0.05), non-IgA mesangial GN (0.027 +/- 0.012, p < 0.05) and those with IgAGN and renal failure (0.032 +/- 0.011, p < 0.01). However no difference was found between MGN patients and normals by deleting MGN cases with mild to moderate mesangial proliferation. The mean value of urinary cGMP in IgAGN patients with renal failure (0.186 +/- 0.117 nmol/min) was lower (p < 0.05) than that of each group with normal renal function (IgAGN: 0.378 +/- 0.010 nM/min; MGN: 0.338 +/- 0.064 nmol/min, non-IgAGN: 0.436 +/- 0.168 nmol/min). The same significant differences were obtained by correcting cGMP values for creatinine urinary excretion. Urinary ET/cGMP ratio (assumed as an index of the relative balance between vasoconstrictor and vasorelaxing factors) was found to be higher than normal (0.570 +/- 0.010 ng/nmol) both in IgAGN patients with normal renal function (0.103 +/- 0.064 ng/mol, p < 0.05), and in those with renal failure (0.203 +/- 0.108 ng/nmol, p < 0.02). Urinary cGMP values were not related to plasma levels of atrial natriuretic peptide (ANP). These data show that hyperexcretion of ET1 occurs in a number of patients with mesangial proliferative GN. In some of them, mainly those with established glomerular damage, the local production of ET1 is not counter-balanced by adequate cGMP biosynthesis.
血管收缩肽内皮素 -1（ET1）直到最近才被明确其特性，目前其作用在很大程度上仍属推测。据推测，ET1作用于系膜细胞，引起血管活性变化，这最终可能导致肾小球硬化的发展。与ET1相反，一氧化氮（NO）可抑制系膜细胞收缩和增殖。NO激活可溶性鸟苷酸环化酶，其最终产物环磷酸鸟苷（cGMP）最近被用作NO作用的标志物。对58例经活检证实为肾小球肾炎（GN）的患者检测了尿ET1和cGMP水平，其中包括36例IgA肾病（IgAGN）患者，30例肾功能正常患者和6例肾功能受损患者，10例非IgA系膜增生性GN患者以及12例肾功能正常的膜性肾病（MGN）患者。与正常对照组（0.019±0.006 ng/分钟）相比，肾功能正常的IgAGN患者（0.035±0.017，p<0.01）、MGN患者（0.028±0.013，p<0.05）、非IgA系膜增生性GN患者（0.027±0.012，p<0.05）以及伴有肾衰竭的IgAGN患者（0.032±0.011，p<0.01）的尿ET1水平显著升高。然而，剔除轻度至中度系膜增生的MGN病例后，MGN患者与正常对照组之间未发现差异。伴有肾衰竭的IgAGN患者尿cGMP的平均值（0.186±0.117 nmol/分钟）低于各肾功能正常组（IgAGN：0.378±0.010 nM/分钟；MGN：0.338±0.064 nmol/分钟，非IgA系膜增生性GN：0.436±0.168 nmol/分钟）（p<0.05）。通过校正尿肌酐排泄量的cGMP值也得到了相同的显著差异。尿ET/cGMP比值（被视为血管收缩因子与血管舒张因子相对平衡的指标）在肾功能正常的IgAGN患者（0.103±0.064 ng/摩尔，p<0.05）和伴有肾衰竭的患者（0.203±0.108 ng/纳摩尔，p<0.02）中均高于正常水平（0.570±0.010 ng/纳摩尔）。尿cGMP值与血浆心房利钠肽（ANP）水平无关。这些数据表明，ET1排泄过多发生在一些系膜增生性GN患者中。其中一些患者，主要是那些已出现肾小球损伤的患者，ET1的局部产生未被足够的cGMP生物合成所抵消。
