Burrell L M, Phillips P A, Risvanis J, Chan R K, Aldred K L, Johnston C I
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg 3084, Victoria, Australia.
Am J Physiol. 1998 Jul;275(1):H176-82. doi: 10.1152/ajpheart.1998.275.1.H176.
The hormone arginine vasopressin (AVP) contributes to water retention and vasoconstriction in congestive heart failure (CHF) through effects at the V2 and V1a receptors, respectively. The effect of long-term V2 receptor (V2R) blockade using OPC-31260 was assessed in a rat model of postinfarction-induced CHF. Rats underwent coronary artery ligation or sham operation and were treated for 6 mo with oral OPC-31260 (10 mg . kg-1 . day-1) or vehicle. CHF was characterized by left ventricular remodeling and impaired systolic function, increased cardiac and lung weight, and elevated plasma atrial natriuretic peptide; plasma AVP and plasma renin activity were not increased. Chronic V2R blockade increased urine volume (P < 0.01) and decreased urine osmolality (P < 0.01) but had no natriuretic effects. V2R blockade did not activate the renin-angiotensin system but increased plasma AVP in CHF (P < 0.01). V2R blockade did not influence cardiac remodeling, cardiac function, or survival. These results suggest that AVP plays a major role in water retention through the renal V2R in a rat model of CHF. V2R blockade using OPC-31260 may represent an alternative to standard diuretic therapy in the management of water retention that characterizes heart failure.
精氨酸加压素（AVP）激素分别通过作用于V2和V1a受体，在充血性心力衰竭（CHF）中促进水潴留和血管收缩。使用OPC - 31260进行长期V2受体（V2R）阻断的效果，在心肌梗死后诱导的CHF大鼠模型中进行了评估。大鼠接受冠状动脉结扎或假手术，并口服OPC - 31260（10 mg·kg-1·天-1）或赋形剂治疗6个月。CHF的特征为左心室重塑和收缩功能受损、心脏和肺重量增加以及血浆心钠素升高；血浆AVP和血浆肾素活性未升高。慢性V2R阻断增加尿量（P < 0.01）并降低尿渗透压（P < 0.01），但无利钠作用。V2R阻断未激活肾素 - 血管紧张素系统，但增加了CHF大鼠的血浆AVP（P < 0.01）。V2R阻断不影响心脏重塑、心脏功能或生存率。这些结果表明，在CHF大鼠模型中，AVP通过肾V2R在水潴留中起主要作用。使用OPC - 31260进行V2R阻断可能是治疗心力衰竭特征性水潴留的标准利尿剂治疗的替代方法。
