Nishida N, Ogura T, Yamauchi T, Hosoya M, Ota Z
Third Department of Internal Medicine, Okayama University Medical School, Japan.
Res Commun Chem Pathol Pharmacol. 1994 May;84(2):143-52.
To elucidate the interaction between the renin-angiotensin system and arginine vasopressin (AVP), we investigated the change in the renal AVP receptor in the spontaneously hypertensive rat (SHR) treated with an angiotensin-converting enzyme (ACE) inhibitor, cilazapril. SHR (age 15 weeks) were given oral cilazapril 10 mg/kg body weight daily for 25 days (ACEI group). Systolic blood pressure was significantly decreased in the ACEI group as compared with the untreated SHRs (control group) after day 2. Urine volume in the ACEI group was 3- to 5-fold higher than that in the control group. Under these conditions, the renal AVP receptor was studied using the radiolabeled receptor assay (RRA) of [3H]-AVP from renal medulla membrane fractions. The serum concentrations of sodium, potassium, chloride, urea nitrogen and creatinine were not significantly different between the two groups. The plasma concentration of AVP in the ACEI group was higher than that in the control group. The dissociation constant (Kd) in the ACEI group was significantly lower than that in the control, although there was no significant change of maximum binding capacity (Bmax) between the two groups. We previously reported that the number of renal AVP receptors decreased in rats with diabetes insipidus which were treated with lithium, suggesting that the change in the AVP receptor is a primary cause of polyuric state induced by lithium. In the present study, the diuretic state and the decrease in blood pressure induced by cilazapril resulted in a marked decrease in the Kd of the renal AVP receptor and an increase in the plasma AVP level. It is suggested that plasma AVP and renal AVP receptors in SHR responded to the diuretic state induced by cilazapril by increasing the secretion and renal receptor affinity. We conclude that the AVP system plays an important role in the regulation of the fluid balance under diuretic conditions caused by ACE inhibitor treatment.
为阐明肾素 - 血管紧张素系统与精氨酸加压素（AVP）之间的相互作用，我们研究了用血管紧张素转换酶（ACE）抑制剂西拉普利治疗的自发性高血压大鼠（SHR）肾AVP受体的变化。15周龄的SHR每日口服10 mg/kg体重的西拉普利，持续25天（ACEI组）。与未治疗的SHR（对照组）相比，第2天后ACEI组的收缩压显著降低。ACEI组的尿量比对照组高3至5倍。在这些条件下，使用来自肾髓质膜部分的[3H]-AVP放射性标记受体测定法（RRA）研究肾AVP受体。两组之间血清钠、钾、氯、尿素氮和肌酐浓度无显著差异。ACEI组的血浆AVP浓度高于对照组。ACEI组的解离常数（Kd）显著低于对照组，尽管两组之间的最大结合容量（Bmax）无显著变化。我们之前报道过，用锂治疗的尿崩症大鼠肾AVP受体数量减少，提示AVP受体的变化是锂诱导多尿状态的主要原因。在本研究中，西拉普利诱导的利尿状态和血压降低导致肾AVP受体的Kd显著降低和血浆AVP水平升高。提示SHR中的血浆AVP和肾AVP受体通过增加分泌和肾受体亲和力对西拉普利诱导的利尿状态作出反应。我们得出结论，在ACE抑制剂治疗引起的利尿条件下，AVP系统在液体平衡调节中起重要作用。
