title: The state and responsiveness of the renin-angiotensin-aldosterone system in patients with type II diabetes mellitus.
abstract: We have recently reported a combination of renal features that suggests independent angiotensin-mediated control of the renal circulation in the majority of hypertensive patients with type II diabetes. To ascertain whether other tissue elements of the renin-angiotensin-aldosterone system (RAAS) also were activated, we examined the adrenal response to angiotensin II (AngII) infusion on a low salt diet. We assessed also the renin response to the upright position in patients on a low salt diet and renin suppression in patients on a high salt diet. We compared responses in 42 hypertensive patients with type II diabetes (53.1 +/- 1.4 years, mean +/- SEM), 25 healthy controls (52.6 +/- 4.4 years); and 137 essential hypertensives without diabetes (43.3 +/- 1.2 years). A low renin state, defined as a plasma renin activity (PRA) <2.5 ng angiotensin I (AI)/mL/h after 5 to 7 days on a 10-mmol Na diet and 2 h of upright posture, was found in 21% of the essential hypertensives, but in only 14% of patients with type II diabetes. On this diet, PRA increased from 2.7 +/- 0.4 supine to 10.1 +/- 1.3 ng AI/mL/h upon standing in healthy subjects. In patients with type II diabetes, PRA was 3.6 +/- 0.4 and increased to 9.1 +/- 1.0 ng AI/mL/h. On a high salt (200 mmol) diet, healthy subjects showed the expected PRA suppression (0.3 +/- 0.1), but in patients with type II diabetes the PRA was less suppressed (1.2 +/- 0.3 ng AI/mL/h; P = .003). Thus, in most hypertensive patients with type II diabetes the RAAS shows normal activation, but is poorly suppressible. AngII infused intravenously to assess adrenal responsiveness in patients on a low salt diet caused an essentially identical increase in aldosterone concentration in patients with type II diabetes (21.1 +/- 1.7 to 44.0 +/- 5.9 ng/dL) and in essential hypertension (20.6 +/- 1.4 to 43.7 +/- 2.8 ng/ dL). The frequency of nonmodulation assessed as a blunted adrenal response to AngII infusion was identical in type II diabetes (47%) and in essential hypertension (46%) after exclusion of the low renin patients. Thus, at the level of one tissue renin system, the adrenal glomerulosa, responses were unaltered in patients with type II diabetes. The relative unresponsiveness of the renal blood supply to infused AngII in type II diabetes in association with an enhanced renal vasodilator response to angiotensin converting enzyme inhibition probably reflects local, intrarenal actions secondary to the diabetic state. The infrequency of a low renin state, and the inappropriately high renin levels on a high salt intake, provide a rational basis for pharmacologic interruption of the renin system to treat patients with type II diabetes.
authors.affiliation: Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Price
authors.forename: J M
authors.initials: JM
authors.lastname: De'Oliveira
authors.forename: N D
authors.initials: ND
authors.lastname: Fisher
authors.forename: G H
authors.initials: GH
authors.lastname: Williams
authors.forename: N K
authors.initials: NK
authors.lastname: Hollenberg
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D004039:Diet, Sodium-Restricted; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications; D008297:Male; D008875:Middle Aged; D011187:Posture; D012083:Renin / Q000097:blood / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000187:drug effects
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000450:Aldosterone; D012083:Renin