Differential expression of KCNQ1 K+ channel in tubular cells of frog kidney

The aim of this study was to evaluate KCNQ1 K+ channel expression in the frog kidney of Rana esculenta. KCNQ1 K+ channel, also known as KvLQT1, is the pore forming α-subunit of the IKs K+ channel, a delayed rectifier voltage-gated K+ channel, which has an important role in water and salt transport in the kidney and gastrointestinal tract. The expression of KCNQ1 K+ channel along tubular epithelium differs from species to species. In the present study the expression of KCNQ1 K+ channel in the frog kidney has been demonstrated by immunohistochemistry. The presence of KCNQ1 K+ channel was demonstrated in the epithelial cells of distal convoluted tubule and collecting duct. However, the pattern of expression of KCNQ1 K+ channel differs between distal convoluted tubules and collecting duct. All epithelial cells of distal convoluted tubules revealed basolateral expression of KCNQ1 K+ channel. On the contrary, only the single cells of collecting duct, probably intercalated cells, showed diffuse cell surface staining with antibodies against KCNQ1 K+ channel. These findings suggest that KCNQ1 K+ channel has cell-specific roles in renal potassium ion transport

L-arginine reduces tubular cell injury in acute post-ischaemic renal failure

Background. The pathophysiology of renal ischaemia, resulting in tubular cell injury and leading to acute renal failure (ARF), remains unclear. An ever-increasing number of investigations focus on a possible role of nitric oxide (NO) in regulating circulation during ARF. In this context, we investigated the influence of chronic stimulation or inhibition of NO synthesis, or both, on haemodynamic parameters, histology and plasma renin activity (PRA) after ischaemia-reperfusion injury of rat kidneys. Methods, Experiments were performed on adult, male Wistar rats. Before induction of ARF, a group of animals was treated with a NO synthesis inhibitor (L-NAME) and another group was treated with a precursor of NO synthesis (L-arginine). The animals received those substances for 4 weeks. Control groups received the same amount of tap water for 4 or 8 weeks and were divided into groups with ARF (4 weeks-ARF group and 8 weeks-ARF group) and a sham-operated group. Another group of rats was treated first with L-NAME and then with L-arginine in their drinking water, for 4 weeks for each of these two substances. All parameters were evaluated 24 h after the induction of ischaemic ARF or the sham operation. Results, Our results show that such long-term stimulation of NO release by L-arginine improved renal haemodynamics in the ischaemic form of ARF. Renal blood Bow (RBF) increased by 96% in the L-arginine-treated rats with ARF compared with the group with ARF alone. Inhibition of NO synthesis worsens renal haemodynamics after ARF. However, this aggravation can be reversed by L-arginine. The rate of water reabsorption was reduced in all groups with ARF, but this reduction was least in the group treated with L-arginine. The rate of Na+ reabsorption was reduced in all groups 24 h after renal ischaemia, but a significant decrease was observed after the inhibition of NO synthesis. Histological examination of the kidney specimens showed that morphological changes were least in the rats treated with L-arginine, when compared with all other groups with ARF. Nevertheless, the lesions were most prominent in the L-NAME + ARF group. In this group, the areas of corticomedullar necrosis were more widespread in comparison with other groups, especially the L-arginine group where only swelling of the proximal tubular cells was observed. Treatment with L-NAME was not accompanied by any significant alteration in the plasma concentration of angiotensin I (ANG I), while in the group treated with L-arginine ANG I had a tendency to decrease. Conclusions. Acute post-ischaemic renal failure may be alleviated by administering the NO substrate (L-arginine). NO acts cytoprotectively on tubular epithelial cells in ischaemia-reperfusion injury of rat kidney. Evidence of this comes from both histopathological findings and increased tubular water and sodium reabsorption. However, inhibition of NO synthesis (provoked by L-NAME) worsens renal haemodynamics and aggravates morphological changes after ARF. These aggravations can, however, be reversed by L-arginine

Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney

Ischemic acute renal failure (ARF) is a highly complex disorder involving renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and generation of reactive oxygen species. Due to this complexity, the aim of our study was to explore effects of Angiotensin II type 1 receptor (AT1R) blockade on kidney structure and function, as well as oxidative stress in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. Experiments were performed on anaesthetized adult male SHR in the model of ARF with 40 minutes clamping the left renal artery. The right kidney was removed and 40 minutes renal ischemia was performed. Experimental groups received AT1R antagonist (Losartan) or vehicle (saline) in the femoral vein 5 minutes before, during and 175 minutes after the period of ischemia. Biochemical parameters were measured and kidney specimens were collected 24h after reperfusion. ARF significantly decreased creatinine and urea clearance, increased LDL and lipid peroxidation in plasma. Treatment with losartan induced a significant increase of creatinine and urea clearance, as well as HDL. Lipid peroxidation in plasma was decreased and catalase enzyme activity in erythrocytes was increased after losartan treatment. Losartan reduced cortico-medullary necrosis and tubular dilatation in the kidney. High expression of pro-apoptotic Bax protein in the injured kidney was downregulated after losartan treatment. Our results reveal that angiotensin II (via AT1R) mediates the most postischemic injuries in hypertensive kidney through oxidative stress enhancement. Therefore, blockade of AT1R may have beneficial effects in hypertensive patients who have developed ARF

Belgrade, Serbia

The aim of this study was to evaluate KCNQ1 K + channel expression in the frog kidney of Rana esculenta. KCNQ1 K + channel, also known as KvLQT1, is the pore forming a-subunit of the IKs K + channel, a delayed rectifier voltage-gated K + channel, which has an important role in water and salt transport in the kidney and gastrointestinal tract. The expression of KCNQ1 K + channel along tubular epithelium differs from species to species. In the present study the expression of KCNQ1 K + channel in the frog kidney has been demonstrated by immunohistochemistry. The presence of KCNQ1 K + channel was demonstrated in the epithelial cells of distal convoluted tubule and collecting duct. However, the pattern of expression of KCNQ1 K + channel differs between distal convoluted tubules and collecting duct. All epithelial cells of distal convoluted tubules revealed basolateral expression of KCNQ1 K + channel. On the contrary, only the single cells of collecting duct, probably intercalated cells, showed diffuse cell surface staining with antibodies against KCNQ1 K + channel. These findings suggest that KCNQ1 K + channel has cell-specific roles in renal potassium ion transport

Angiotensin 2 type 1 receptor blockade different affects postishemic kidney injury in normotensive and hypertensive rats

Many studies demonstrated that angiotensin 2 type 1 receptor (AT1R) blockade accelerates renal recovery in post-ischaemic kidney but there are many controversies related to its net effect on kidney structure and function. During the past years, our research group was trying to define the pathophysiological significance of the renin-angiotensin system on post-ischemic acute renal failure (ARF) development in normotensive Wistar as well as hypertensive rats (SHR). This review mostly summarizes our experience in that field. Our previous studies in normotensive rats revealed that AT1R blockade, except slightly renal vascular resistance improvement, had no other obvious beneficial effects, and therefore implies angiotensin 2 (Ang-2) overexpression as non-dominant on kidney reperfusion injuries development. Similarly it was observed in Wistar rats with induced mild (L-NAME, 3 mg/kg b.w.) nitric oxide (NO) deficiency. Expectably, in strong induced (L-NAME, 10 mg/kg b.w.) NO deficiency associated with ARF, massive tubular injuries indicate harmful effects of AT1R blockade, implying strongly disturbed glomerular filtration and suggesting special precaution related to AT1R blockers usage. Opposite to previous, by our opinion, AT1R antagonism promises new advance in treatment of essentially hypertensive subjects who develop ARF. Increased glomerular filtration, diminished oxidative stress, and most importantly improved tubular structure in postishemic SHR treated with AT1R blocker losartan, implicate Ang-2 over production as potently agent in the kidney ischemic injury, partly trough generation of reactive oxygen species. These data contribute understanding the pathogenesis of this devastating illness in hypertensive surroundings