Effect of oxygen derived free radicals and glycine on sodium-potassium adenosine triphosphatase in the basolateral membrane of the kidney in ischemia-reperfusion

The aim of the present study was to examine the effect of exposing rats to ischemia-reperfusion while breathing 100% oxygen or room air, to find the effect of glycine on renal sodium-potassium adenosine triphosphatase [Na +/- K+ATPase] and endogenous antioxidant enzymes, superoxide dismutase and catalase, also to ascertain the effect of ischemia-reperfusion on renal nitric oxide and lipid peroxides. This study was carried out at King Saud University, Riyadh, Kingdom of Saudi Arabia, over a period of 11 months, February to December 2001. All previous measurements were carried out on the renal homogenate after 60 minutes ischemia, then after reperfusion while animals breathed room air or 100% oxygen and also after glycine treatment. The activity of Na +/- K+ATPase, catalase and superoxide dismutase concentration was decreased significantly in the ischemic rats compared to the control, a further decrease was found after 20 minutes of reflow while breathing room air. Breathing 100% oxygen resulted in a significant decrease in catalase and Na +/- K+ATPase activity and concentration of superoxide dismutase, glycine caused insignificant change of these enzymes after ischemia-index of lipid peroxidation and nitric oxide they were significantly elevated following reperfusion while rats breathed room air and further elevation was noticed after breathing 100% oxygen. However, potassium and creatinine did not change in all study groups, showed significant decrease after ischemia and ischemia-reperfusion may be due to marked Na+ loss in urine and lack of Na+ reabsorption. The inhibition of superoxide dismutase and catalase can be explained by increased reactive oxygen species during reperfusion and hyperoxia, also due to nitric oxide production and lipid peroxidation as shown by high malondialdehyde. Lack of Na+K+ATPase can be contributed to loss of antioxidant enzymes, nitric oxide production, and high reactive oxygen species. Hyperoxia in ischemia-reperfusion induces severe damage to cellular defence mechanisms and enhances reactive oxygen species injury. Glycine, as antioxidant, is involved in kidney protection from massive injury induced by ischemia-reperfusion, protects renal antioxidant enzymes and Na +/- K+ATPase, normalizes malondialdehyde, and nitric oxide levels. This data further supports the possible role of glycine therapy as an adjunct in the treatment of renal failure

Effects of prolonged blockade of endothelium derived nitric oxide and its treatment in the gravid rats

The endothelial derived nitric oxide is believed to be involved in many physiological adaptations during normal pregnancy e.g. vasodilatation of the maternal systemic circulation, increased fetoplacental blood/flow and uterine quiescence before parturition. The pathogenesis of the maternal syndrome of pre-eclampsia is presumed to be due to generalized maternal endothelial cell dysfunction. The purpose of our study was to investigate the role of the endothelial nitric oxide deficiency in the physiopathology of pre-eclampsia and if the treatment with L-arginine prevents pre-eclampsia. Thirty pregnant rats of the same weight [200-250 gms] were divided into 3 groups, group I [10 pregnant rats used as control, they were injected daily with IV saline from the 10th day of gestation, till the day after labour], group II [10 pregnant rats injected daily with L-NAME to inhibit nitric oxide synthesis, starting from the 10th day of gestation and continued as in group I] group III [10 pregnant rats received L-arginine in the drinking water and injected with L-NAME as in group II]. The following results were obtained 9 days after starting injection, a significant decrease of platelets count, pups weight [weight of newborn rats] and body weight of mothers in group II compared to group I. The urine volume, urinary albumin, urinary sodium, urinary gamma-glutamyl transferase, hematocrite% and mean arterial blood pressure were significantly elevated in L-NAME treated rats [group II]. One day after delivery the mean arterial blood pressure in group II rapidly declined and showed insignificant change compared to group I. In group III L-arginine reverses the effects of L-NAME, and gives results resembling those of controls. The findings are consistent with the concept that not only a generalized endothelial dysfunction is involved in the pathogenesis of pre-eclampsia, but also deficient production of endothelial derived nitric oxide, the impaired nitric oxide production could contribute to hypertension, thrombocytopenia, albuminuria, diuresis, natriuresis and intrauterine growth retardation, which are manifestations of pre-eclampsia. The finding that L-arginine prevents development of pre-eclampsia lend support to the therapeutic use of NO donors in prevention of pre-eclampsia

Study of the effect of central administration of prostigmine and atropine on the exercise pressor reflex in anesthetized rats

This study included 20 rats, exposed to muscular manipulation in the form of static contraction and passive stretch of triceps surae muscle. These manipulations increased e basal MAP and HR [exercise pressor reflex]. Central prostigmine injection had not any effect on the resting MAP and HR. Prostigmine inhibited the contraction evoked responses of the MAP and HR, also it blunted the MAP and HR response to passive stretch. Then the rats were divided into two groups, group I included 10 rats, in this group the rats are left 90-120 min after prostigmine injection, this is considered as a recovery period, the cardiovascular responses to muscular manipulation are returned to normal responses after this recovery period, the muscular manipulation caused a significant increase of both MAP and HR. Group II of ten rats exposed to central administration of atropine [muscurinic antagonist] and one hour later prostigmine was injected centraly, atropine blocked the prostigmine inhibitory effect on the MAP and HR in response to muscular manipulation. Muscular contraction and passive stretch in this group caused a significant increase of MAP and HR. These results suggest that central cholinergic system stimulation could inhibit the exercise pressor reflex in the anesthetized rats