Efeitos da uroguanilina em túbulo proximal de ratos submetidos à doença renal crônica experimental

Abstract

Chronic kidney disease (CKD) is a major public health problem that affects mainly Western countries. In the context of the pathophysiology of this condition, the level of natriuretic peptides, such as atrial natriuretic peptChronic kidney disease (CKD) is a major public health problem that affects mainly Western countries. In the context of the pathophysiology of this condition, the level of natriuretic peptides, such as atrial natriuretic peptide (ANP) and uroguanylin (UGN), are elevated. However, it is not known whether high levels of these hormones imply in suitable natriuretic response. In addition, studies are required to establish a relationship between CKD and regulation of natriuretic peptides and a possible relationship with angiotensin II (AngII). Thus, we attempted to evaluate a possible modulation of the UGN response by enalapril in the 5/6 nephrectomy model (nx 5/6). Male Wistar rats weighing 250-300g were used. The animals were divided in 4 groups (n = 8): control groups without treatment or treated with enalapril (10mg / kg) (SHAM and SHAM + E) and groups submitted to nx 5/6 without treatment or treated with enalapril (10 mg / kg vol) (Nx and Nx + E). At the end of the 10th week after surgery, the animals were submitted to stationary microperfusion technique in vivo, in order to investigate the role of UGN in the proximal tubule in face of the different conditions. Subsequently, some markers of renal function and oxidative stress were determined, as well as urinary GMPc levels. Nx presented increased serum creatinine, urea, proteinuria, sodium excretion fraction (FENa+) and malonaldehyde (MDA), and glomerular filtration rate (GFR), as well as decreased superoxide dismutase activity (SOD). Nx + E, when compared to Nx, presented reduced levels of creatinine, urea, proteinuria, FENa +, and MDA, in addition to elevating GFR. The CKD group had low urinary cGMP levels compared to controls, and the enalapril group partially attenuated this reduction. Through the stationary microperfusion technique, a decrease in proximal tubular reabsorption of bicarbonate was observed in animals submitted to nx 5/6. Intratubular infusion of UGN did not show any response in the animals with CKD, suggesting insensitivity of the proximal tubule to this hormone in this condition. On the other hand, in the Nx + E group the UGN presented inhibitory character on the bicarbonate reabsorption flow. Thus, it is suggested that the modulation of the RAAS in DRC increase the sensitivity of the GC-C receptor to the UGN at the renal level.