Prevention of kidney haemorrhagic necrosis of choline-deficient rats by alpha-methyldopa treatment.

In a previous report from our laboratory we have shown a marked increase in the levels of renal catecholamines in choline-deficient rats in comparison to choline-supplemented animals, while the content of acetylcholine remained unchanged. Since the changes in tissue catecholamines occurred before kidney lesions developed, we have suggested that an imbalance between sympathetic and parasympathetic systems plays an important role in the pathogenesis of renal injury in choline-deficient rates, this imbalance being the result of an excess of catecholamines in the kidneys. A series of experiments was then planned to explore this theory further by administering adrenergic blocking agents in an attempt to prevent the development of the renal injury in choline deficiency. We report here our results on the administration of α-methyldopa, a drug that depletes the tissue stores of catecholamines, to choline-deficient and choline-supplemented rats. Young male Wistar rats were divided at random into 4 groups: Group CS, fed a choline-supplemented diet; Group CS + D, fed a choline-supplemented diet and treated with α-methyldopa; Group CD, fed a choline-deficient diet; and Group CD + D, fed a cholinedeficient diet and treated with α-methyldopa. The appropriate groups received daily i.p. injections of α-methyldopa (300 mg/kg body wt). The kidneys of all surviving rats were studied grossly and histologically, and the levels of noradrenaline and adrenaline determined. All animals from Control Groups CS and CS + D showed essentially normal kidneys on gross and light microscopic examination. On the other hand, CD rats showed marked renal injury, while the kidneys lesions of CD + D animals were significantly less pronounced than those of rats from Group CD. The total content of noradrenaline and adrenaline in the kidneys of CD + D and CD rats were not statistically different, although the CD + D animals tended to have lower levels of catecholamines. The content of noradrenaline and adrenaline of rats from Group CD was significantly higher than the corresponding values in CS rats. Also, the total content of renal noradrenaline of CD + D animals was found to be unaltered when compared to that of CS rats, while their content of adrenaline was found to be higher than the corresponding value in CS group. The noradrenaline levels of CS and CS + D rats were similar, but the latter group had a higher renal adrenaline content than the former. These findings, besides confirming our previous observations, clearly show that α-methyldopa afforded a protective effect against the renal injury of choline deficiency, thus giving strong additional support to the theory that the kidney haemorrhagic necrosis of choline deficiency in young rats is probably due to an autonomic imbalance.