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

Background. The pathophysiology of renal ischaemia, resulting in tubular ce ll injury and leading to acute renal failure (ARF), remains unclear. An eve r-increasing number of investigations focus on a possible role of nitric ox ide (NO) in regulating circulation during ARF. In this context, we investig ated 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 indu ction 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 group s received the same amount of tap water for 4 or 8 weeks and were divided i nto groups with ARF (4 weeks-ARF group and 8 weeks-ARF group) and a sham-op erated 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 ischa emic 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 c ompared with the group with ARF alone. Inhibition of NO synthesis worsens r enal haemodynamics after ARF. However, this aggravation can be reversed by L-arginine. The rate of water reabsorption was reduced in all groups with A RF, 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 ischaem ia, but a significant decrease was observed after the inhibition of NO synt hesis. Histological examination of the kidney specimens showed that morphol ogical changes were least in the rats treated with L-arginine, when compare d with all other groups with ARF. Nevertheless, the lesions were most promi nent 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 alte ration in the plasma concentration of angiotensin I (ANG I), while in the g roup treated with L-arginine ANG I had a tendency to decrease. Conclusions. Acute post-ischaemic renal failure may be alleviated by admini stering 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 wate r and sodium reabsorption. However, inhibition of NO synthesis (provoked by L-NAME) worsens renal haemodynamics and aggravates morphological changes a fter ARF. These aggravations can, however, be reversed by L-arginine.