Buemi Michele, Nostro Lorena, Di Pasquale Giuseppe, Cavallaro Emanuela, Sturiale Alessio, Floccari Fulvio, Aloisi Carmela, Ruello Antonella, Calapai Gioacchino, Corica Francesco, Frisina Nicola
Nephrology, Department of Internal Medicine, University of Messina, Messina, Italy.
Am J Hypertens. 2004 Dec;17(12 Pt 1):1170-8. doi: 10.1016/j.amjhyper.2004.07.003.
Vasopressin (AVP), an antidiuretic hormone, is known to induce hypervolemia and to regulate the renal expression of aquaporin-2 (AQP2) water channels, but it is not yet known whether the latter are involved in the pathogenesis of essential hypertension. The aim of the present study was therefore to make a comparative study of blood pressure (BP), urinary volume (UV), urinary osmolarity (uOsm), urinary AQP2 (uAQP2), and plasma AVP levels (PAVP) in male spontaneously hypertensive rats (SHR; n = 30) at 3, 7, and 12 weeks of age and in male Wistar-Kyoto rats (WKY, n = 30), also after the subcutaneous administration of OPC-31260 (OPC), a human AVP V(2) receptor antagonist. At 3 weeks, SHR had markedly higher uOsm and lower UV levels than WKY. At 7 weeks, SHR were hypertensive, showing increased uAQP2, PAVP, and uOsm levels and a decreased UV. At 12 weeks, no significant changes were observed in this condition. At 7 and 12 weeks of age, OPC-treated WKY rats showed significant reduction in BP and uOsm and increase in UV with respect to untreated animals. From 3 weeks of age, OPC-treated SHR presented significantly lower BP levels, higher UV levels, and lower uOsm than untreated animals. In treated WKY and SHR, uAQP2 levels were lower than in untreated animals. The PAVP appeared to be higher in OPC-treated rats from both strains. These findings suggest that AVP and the AQP2 are involved in the pathogenesis of hypertension in SHR.
抗利尿激素血管加压素(AVP)可引起血容量过多并调节水通道蛋白2(AQP2)水通道的肾脏表达,但后者是否参与原发性高血压的发病机制尚不清楚。因此,本研究的目的是比较雄性自发性高血压大鼠(SHR;n = 30)在3、7和12周龄时以及雄性Wistar-Kyoto大鼠(WKY,n = 30)皮下注射人AVP V(2)受体拮抗剂OPC-31260(OPC)后的血压(BP)、尿量(UV)、尿渗透压(uOsm)、尿AQP2(uAQP2)和血浆AVP水平(PAVP)。3周时,SHR的uOsm明显高于WKY,UV水平低于WKY。7周时,SHR出现高血压,uAQP2、PAVP和uOsm水平升高,UV降低。12周时,此情况未观察到显著变化。在7周和12周龄时,OPC处理的WKY大鼠与未处理的动物相比,血压和uOsm显著降低,UV增加。从3周龄开始,OPC处理的SHR与未处理的动物相比,血压水平显著降低,UV水平升高,uOsm降低。在处理过的WKY和SHR中,uAQP2水平低于未处理的动物。两种品系经OPC处理的大鼠PAVP似乎更高。这些发现表明,AVP和AQP2参与了SHR高血压的发病机制。