Igaki T, Itoh H, Suga S, Hama N, Ogawa Y, Komatsu Y, Mukoyama M, Sugawara A, Yoshimasa T, Tanaka I, Nakao K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Kidney Int Suppl. 1996 Jun;55:S144-7.
We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells and acts as an endothelium-derived relaxing peptide. To clarify the clinical significance of CNP in renal disorders, we examined the plasma level of CNP in patients with various cardiovascular diseases, including chronic renal failure (CRF) patients who were under hemodialysis therapy. We also investigated biological effects of intravenously-administered CNP (0.43 nmol/kg) by bolus injection from the peripheral vein in healthy volunteers and measured systemic hemodynamic variables, plasma levels of CNP, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cGMP, aldosterone and also urine volume, urinary excretions of sodium, potassium, chloride and cGMP. The plasma CNP levels in healthy humans (N = 13) was 1.4 +/- 0.6 fmol/ml. In CRF patients, the plasma CNP significantly increased up to 3.0 +/- 1.1 fmol/ml. The administration of CNP elicited significant increase of plasma cGMP level (from 4.77 +/- 1.25 to 8.33 +/- 1.59 pmol/ml 15 min after the administration) and of urinary cGMP excretion (from 30.7 +/- 4.3 to 74.9 +/- 13.4 nmol/30 min). Intravenously-administered CNP exerted significant diuretic (% increase: +117 +/- 85.0), natriuretic, kalliuretic and chloriuretic actions with the increase of endogenous creatinine clearance. CNP also elicited significant hypotensive actions (delta BPs/delta BPd: -4.3 +/- 1.3/-4.1 +/- 1.0 mm Hg) with the concomitant increase of heart rate (+7.6 +/- 2.6 bpm). Plasma aldosterone concentration significantly decreased from 45.4 +/- 2.3 to 35.4 +/- 4.9 pg/ml 30 minutes after the administration. Taken together, these results suggest a role for CNP in human renal function.
我们之前曾报道，利钠肽家族的第三个成员C型利钠肽（CNP）在血管内皮细胞中产生，并作为一种内皮源性舒张肽发挥作用。为了阐明CNP在肾脏疾病中的临床意义，我们检测了各种心血管疾病患者的血浆CNP水平，包括接受血液透析治疗的慢性肾衰竭（CRF）患者。我们还通过外周静脉推注，研究了静脉注射CNP（0.43 nmol/kg）对健康志愿者的生物学效应，并测量了全身血流动力学变量、血浆CNP、心房利钠肽（ANP）、脑利钠肽（BNP）、环磷酸鸟苷（cGMP）、醛固酮水平以及尿量、尿钠、钾、氯和cGMP的排泄量。健康人（N = 13）的血浆CNP水平为1.4±0.6 fmol/ml。在CRF患者中，血浆CNP显著升高至3.0±1.1 fmol/ml。注射CNP后，血浆cGMP水平显著升高（给药后15分钟从4.77±1.25升至8.33±1.59 pmol/ml），尿cGMP排泄量也显著增加（从30.7±4.3升至74.9±13.4 nmol/30分钟）。静脉注射CNP具有显著的利尿作用（增加百分比：+117±85.0）、利钠、利钾和利氯作用，同时内源性肌酐清除率增加。CNP还引起显著的降压作用（收缩压变化/舒张压变化：-4.3±1.3/-4.1±1.0 mmHg），同时心率增加（+7.6±2.6次/分钟）。给药30分钟后，血浆醛固酮浓度从45.4±2.3显著降至35.4±4.9 pg/ml。综上所述，这些结果表明CNP在人类肾功能中发挥作用。
