Reduced abundance of aquaporins in rats with bilateral ischemia-induced acute renal failure: prevention by α-MSH

Abstract

We examined the effect of temporary renal ischemia (30 min or 60 min) and reperfusion (1 day or 5 days) on the expression of renal aquaporins (AQPs) and urinary concentration in rats with bilateral ischemia-induced acute renal failure (ARF). Next, we tested whether reducing ischemia/reperfusion (I/R) injury by treatment with α-melanocyte stimulating hormone (α-MSH) affects the expression of AQPs and urine output. Rats with ARF showed significant renal insufficiency, and urinary concentration was markedly impaired. In rats with mild ischemic injury (30 min), urine output increased significantly to a maximum at 48 h, and then nearly normalized within 5 days. Consistent with this, semiquantitative immunoblotting revealed that kidney AQP1 and AQP2 abundance was significantly decreased after 24 h to 30 ± 5% and 40 ± 11% ( n = 8) of controls ( n = 9), respectively ( P < 0.05). Five days after ischemia, AQP2 abundance was not significantly decreased and urine output was normalized. In contrast, severe ischemic injury (60 min) resulted in a marked reduction in urine output at 24 h, despite a significant decrease in urine osmolality and solute-free water reabsorption, TcH2O. AQP1 and AQP2 abundance was markedly decreased to 51 ± 5% and 31 ± 9% ( n = 10) of controls ( n = 8) at 24 h ( P < 0.05). After 5 days, the rats developed gradually severe polyuria and had very low AQP2 and AQP1 levels [11 ± 4% and 6 ± 2% ( n = 5) of controls ( n = 8), respectively; P < 0.05]. A similar reduction was observed for AQP3. The reduction in AQP expression in the proximal tubule and inner medullary collecting duct was confirmed by immunocytochemistry. Next, we found that intravenous α-MSH treatment of rats with ARF significantly reduced the ischemia-induced downregulation of renal AQPs and reduced the polyuria. In conclusion, the I/R injury is associated with markedly reduced expression of the collecting duct and proximal tubule AQPs, in association with an impairment of urinary concentration. Moreover, α-MSH treatment significantly prevented the reduction in expression of AQPs and renal functional defects. Thus decreased AQP expression is likely to contribute to the impairment in urinary concentration in the postischemic period.

Rehmannia glutinose Ameliorates Renal Function in the Ischemia/Reperfusion-Induced Acute Renal Failure Rats

“…Among the multiple isoforms of AQP water channels, AQP 2 is dominant isoform in the collecting duct of the kidney. 14,19) The present study shows that the expression levels of AQP 2 in the inner and outer medullae and cortex of the kidney were significantly decreased in rats with ischemia/reperfusion-induced ARF rats. These results indicate that decreased level of renal AQP 2 may contribute to impairment in urinary concentration ability in rats with ischemia/reperfusion-induced ARF.…”

“…These findings are not different from previously published data in which marked changes in renal function has been identified in the ischemia-ARF. 13,14) Water excretion is dependent on the balance between the GFR and the net rate of water absorption along the renal tubule. The present study shows that ischemia/reperfusion-induced ARF is characterized by nonoliguria in spite of reduction in creatinine clearance.…”

“…In fact, it was well documented that ischemia-ARF is associated with increased urine flow due to suppression of tubular water reabsorption. 13,14) One important factor in this decrease in tubular water reabsorption is the osmotic diuresis that may accompany the elimination of urea and other species that accumulated in the blood due to the renal failure. The other important factor is the decreased expression of AQP 2 water channel that is responsible for the ability of water to penetrate the collecting duct epithelium, thus returning water to the blood stream in response to vasopressin.…”

“…[13][14][15] Although ARR is widely used in Oriental medicine for the treatment of renal diseases, there is little experimental data about beneficial effects of ARR on renal diseases in vivo. Moreover, ARR is the most important component in the Yukmijihwang-tang (called 'liuweidihuang-tang' in China) of which Oriental medicinal decoction consists of six medicinal plants used for the treatment of renal diseases.…”

Renal Effects of Plant-Derived Oleanolic Acid in Streptozotocin-Induced Diabetic Rats

“…[15,16,[24][25][26] Low GFR is associated with fluid and electrolyte imbalance in nephrotic syndrome [27] and acute renal failure. [28][29][30] It is therefore speculated that OA administration significantly improved renal function of STZ-induced diabetic rats, perhaps in part mediated via the elevation of GFR. We suggest that elevated GFR possibly increased the filtered load of Na + in the tubular filtrate, thereby facilitating urinary Na + excretion.…”