The renin-angiotensin system and catecholamines were evaluated in short term alloxan diabetic rats which were either “severely diabetic” (polyuric with serum glucose > 450 mg. per 100 ml.) or “mildly diabetic” (normouric with serum glucose <450 mg. per 100 ml.). Plasma renin activity (PRA), renal renin activity (RRA), and the amount of angiotensin II producing an acute 10 mm Hg increase in blood pressure were all significantly decreased in the diabetic rats with this decrease correlating inversely with the severity of the diabetes. Insulin treatment of these rats resulted in partial normalization of angiotensin II responsiveness, PRA, and blood urea nitrogen. Injection of alloxan directly into the left renal artery did not decrease RRA. Protection of the left kidney during systemic alloxan injection did not prevent the decrease in renal renin activity. Streptozotocin-treated diabetic rats had increased vascular responsiveness to injected angiotensin II. Norepinephrine sensitivity (amount producing a 10 mm Hg increase in blood pressure) and norepinephrine stores (blood pressure response to tyramine) were normal in both alloxan- and streptozotocin-treated rats.

Blood volume as related to lean body mass was elevated in the severely diabetic rats thus suggesting one possible mechanism for the decrease in the renin-angiotensin system.

These results suggest that (1) norepinephrine responsiveness and norepinephrine stores are normal, and (2) there is suppression of RRA leading to decreased PRA and increased vascular reactivity to angiotensin II in the acutely diabetic alloxan-treated rat. Further, these abnormalities appear to be related to the degree of diabetes as assessed by serum glucose and twenty-four hour urine volume.

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