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To prove the independence of local tissue renin–angiotensin system (RAS) in brain from classical kidney RAS, we measured local angiotensin levels in bilaterally nephrectomized rats which had been dialyzed with a dialysis technique to greatly prolong survival time.Two groups of animals were used: (1) bilaterally nephrectomized rats with intraperitoneal dialysis, where both kidneys were surgically removed; and (2) controls with intact kidneys and dialysis. By using this protocol, we were able to study plasma and brain angiotensins 5 days after nephrectomy (no longer periods have been attempted).Plasma sodium, potassium and pH were monitored while rats were dialyzed four times a day. Plasma samples and brain areas were obtained and angiotensin II measured by radioimmunoassay and high-pressure liquid chromatography (HPLC).Plasma angiotensin II was significantly diminished in the nephrectomized rats but was still detectable, the levels being above the minimal detectable value. The identity of angiotensin I and angiotensin II detected by radioimmunoassay was confirmed by HPLC. In the brain, angiotensin II content was significantly increased in all areas studied. The highest increments were in hypothalamus and brain stem.Our results demonstrate that: (1) brain angiotensin II is regulated independently of peripheral angiotensin II; and (2) a reduced plasma angiotensin II persists 5 days after bilateral nephrectomy. We conclude that the angiotensin II in the plasma was derived from non-renal tissue and the results support the conclusion that tissue RAS has paracrine and autocrine functions independent of the endocrine function of circulating plasma angiotensin.