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Abstract

We have documented, contrary to expectation, that the renin-angiotensin-aldosterone system (RAAS) is stimulated normally by restriction of sodium intake in patients with Type 2 diabetes mellitus (DM) and hypertension. Conversely, plasma renin activity (PRA) is suppressed less than in normal subjects by a high-salt diet in these patients. Increasing plasma angiotensin II (Ang II) concentration through intravenous Ang II infusion also suppresses renin release, via the short feedback loop. In this study, we sought to ascertain whether the limited renin suppression in Type 2 diabetes mellitus via high-salt intake is a unique defect or part of a more generalised abnormality of PRA suppression. We studied 38 patients with Type 2 DM and hypertension, 158 hypertensive control patients, and 61 normotensive controls. All patients were studied while in metabolic balance on a 10 mEq sodium (Na) diet. The response to the Ang II infusion at 3 ng/kg/min for 45 minutes was measured. We found that PRA fell significantly in normal subjects, from 4.0±0.33 to 2.5±0.23 ng AngI/ml/hr (p=0.0056). In patients with essential hypertension, the Ang II infusion also led to a fall in PRA from 3.51±0.23 to 2.76±0.17 ng AngI/ml/hr (p=0.014). In patients with DM, despite a similar basal PRA (3.7±0.40 ng AngI/ml/hr), the infusion of Ang II did not influence PRA significantly (3.43±0.42 ng AngI/ml/hr; p>0.77), though these patients had the most robust mean arterial pressure response. Our data are in complete accord with the concept of high intrarenal Ang II in DM and suggest lower systemic Ang II despite comparable PRA.

Keywords

Type 2 DM PRA angiotensin II

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Blunted suppression of plasma renin activity in diabetes

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