Okada H, Suzuki H, Kanno Y, Saruta T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
J Cardiovasc Pharmacol. 1995 May;25(5):847-52. doi: 10.1097/00005344-199505000-00023.
Effects of novel, nonpeptide vasopressin V1 and V2 receptor antagonists on partially nephrectomized and salt-loaded spontaneously hypertensive rats (SHR), which develop severe hypertension and progressive nephrosclerosis, were investigated. SHR were 5/6-nephrectomized and fed a high salt diet. The rats were divided into four groups: group 1 was an untreated control, group 2 received the V1 antagonist OPC-21268, group 3 received the V2 antagonist OPC-31260, and group 4 received both the V1 and V2 antagonists. The V1 antagonist alone or combined with the V2 antagonist significantly decreased the increase in blood pressure (BP) of groups 2 and 4 rats, but the V2 antagonist alone did not reduce the increase in BP of the group 3 rats. The V2 antagonist alone or combined with the V1 antagonist induced a significant diuresis of rats in groups 3 and 4. The increase in urinary protein excretion and the progression of renal hyaline arteriolosclerosis were attenuated by the V1 antagonist with or without the V2 antagonist in rats in groups 2 and 4, but not by the V2 antagonist alone in rats in group 3. This implies that the progressive nephrosclerosis in SHR with partial renoablation and salt-loading was associated with V1 agonism.
研究了新型非肽类血管加压素V1和V2受体拮抗剂对部分肾切除并高盐喂养的自发性高血压大鼠（SHR）的影响，这类大鼠会发展为严重高血压和进行性肾硬化。对SHR进行5/6肾切除并给予高盐饮食。将大鼠分为四组：第1组为未治疗的对照组，第2组给予V1拮抗剂OPC - 21268，第3组给予V2拮抗剂OPC - 31260，第4组给予V1和V2拮抗剂。单独使用V1拮抗剂或与V2拮抗剂联合使用均显著降低了第2组和第4组大鼠的血压升高，但单独使用V2拮抗剂并未降低第3组大鼠的血压升高。单独使用V2拮抗剂或与V1拮抗剂联合使用均使第3组和第4组大鼠产生显著利尿作用。第2组和第4组大鼠单独使用V1拮抗剂或与V2拮抗剂联合使用均可减轻尿蛋白排泄增加和肾透明小动脉硬化的进展，但第3组大鼠单独使用V2拮抗剂则无此作用。这表明部分肾切除并高盐喂养的SHR中的进行性肾硬化与V1激动作用有关。
