Yamada K, Nakano H, Nishimura M, Yoshida S
Division of Clinical Research, Sakura National Hospital, Chiba, Japan.
J Diabetes Complications. 1995 Oct-Dec;9(4):326-9. doi: 10.1016/1056-8727(95)80033-b.
We examined the effect of an orally effective, nonpeptide AVP.V1-receptor antagonist, OPC21268, on urinary albumin excretion and renal hemodynamics in non-insulin dependent diabetes mellitus (NIDDM) patients (seven patients with microalbuminuria, four with overt nephropathy, and three with normoalbuminuria) and in three normal subjects. The oral administration of 100 mg of OPC21268, which is sufficient to suppress the vasoconstriction induced by exogenously infused AVP, caused a significant decrease in urinary albumin excretion only in NIDDM with microalbuminuria concomitantly with a slight decrease in filtration fraction and glomerular filtration rate (GFR). On the other hand, urinary beta 2 microglobulin excretion did not change at all during the study. Neither change in systemic blood pressure, in heart rate, nor in plasma vasoactive substance levels (ANP, renin activity, aldosterone, and AVP) was observed in all four groups. In conclusion, in NIDDM patients with microalbuminuria, an increase in the sensitivity of contraction of glomerular efferent arterioles via an activation of AVP.V1-receptor(s) is at least present, and AVP.V1-receptor antagonist causes a decrease in urinary albumin excretion due partly to decrease the intraglomerular capillary pressure. This compound may be useful for the treatment of NIDDM microalbuminuria.
我们研究了口服有效的非肽类精氨酸加压素 V1 受体拮抗剂 OPC21268 对非胰岛素依赖型糖尿病（NIDDM）患者（7 例微量白蛋白尿患者、4 例显性肾病患者和 3 例正常白蛋白尿患者）及 3 名正常受试者尿白蛋白排泄和肾血流动力学的影响。口服 100 mg OPC21268（足以抑制外源性输注精氨酸加压素引起的血管收缩）仅使伴有微量白蛋白尿的 NIDDM 患者的尿白蛋白排泄显著减少，同时滤过分数和肾小球滤过率（GFR）略有下降。另一方面，在研究期间尿β2微球蛋白排泄完全没有变化。在所有四组中均未观察到全身血压、心率或血浆血管活性物质水平（心房钠尿肽、肾素活性、醛固酮和精氨酸加压素）的变化。总之，在伴有微量白蛋白尿的 NIDDM 患者中，至少存在通过激活精氨酸加压素 V1 受体使肾小球出球小动脉收缩敏感性增加的情况，并且精氨酸加压素 V1 受体拮抗剂导致尿白蛋白排泄减少部分是由于肾小球内毛细血管压力降低。这种化合物可能对治疗 NIDDM 微量白蛋白尿有用。
