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Biomedical subjects

A R Christlieb

Publications and source records attributed to A R Christlieb.

At least 37 records · Page 2Linked to original sources
PubMed1979

Renin-angiotensin system in phlorhizin compared with alloxan diabetes in the rat.

In alloxan-treated diabetic rats, plasma renin activity (PRA) is decreased. One possible mechanism that may explain the decreased PRA is an increased delivery of sodium to the macula densa produced by the glucose osmotic diuresis, resulting in decreased renin release. To evaluate this possible mechanism, rats with phlorhizin diabetes, which produces a glucose osmotic diuresis without hyperglycemia, were studied and compared with rats with alloxan-induced diabetes. Whereas phlorhizin-treated rats had low blood glucose and alloxan-treated rats had elevated glucose, the glucose osmotic diuresis was similar in the two groups. PRA and plasma renin concentration (PRC) were significantly increased in the phlorhizin group. In the alloxan group, PRA was decreased and angiotensin II sensitivity increased, both significantly. Plasma renin substrate (PRS) remained adequate in each group. These results suggest that the decreased PRA in alloxan-induced diabetes is due neither to factors associated with the glucose osmotic diuresis including changes in renal tubular sodium not to decreased PRS.

Alloxan↗
PubMed1978

Aldosterone responsiveness in patients with diabetes mellitus.

Plasma aldosterone (PA) and plasma renin activity (PRA) were determined in 44 diabetics, of whom nine were normotensive but not nephropathic (group 1), 10 were hypertensive but not nephropathic (group 2), and 25 were hypertensive and nephropathic (group 3); they were kept in balance on a diet composed of 10 to 20 mEq. of sodium (Na) and 100 mEq. of potassium (K). Supine PA in group 1 was 38 +/- 7 ng. per deciliter, whereas in normals it was 24 +/- 2 ng. per deciliter (P less than 0.05); beyond that, neither supine nor upright PA or PRA differed significantly from normal in groups 1 and 2. By contrast, in group 3, supine PA was 13 +/- 1 ng. per deciliter and PRA 2.0 +/- 0.2 ng./ml. and upright PA was 39 +/- 7 ng. per deciliter and PRA 3.8 +/- 0.5 ng./ml., all significantly lower than those in the other groups (P less than 0.01). Nine patients, one in group 1 and eight in group 3, had low supine and upright PA and PRA; four had hyperkalemia. An additional nine patients in group 3 had low upright PA, with normal or low PRA; two had hyperkalemia. Of the 18 patients with low upright PA, K correlated with glucose (R = 0.46, P less than 0.05). These results suggest (1) the renin-aldosterone system generally responds normally in diabetics without nephropathy but responds subnormally when nephropathy is present, (2) hyporeninemic hypoaldosteronism is frequent in diabetics with nephropathy but may occur in the absence of clinical nephropathy, and (3) hyperkalemia in some diabetic patients may be secondary to hypoaldosteronemia and hyperglycemia.

Aldosterone↗
PubMed1976

Big renin and biosynthetic defect of aldosterone in diabetes mellitus.

To determine the cause of selective aldosterone deficiency in two patients with diabetes mellitus, studies of renin and of aldosterone-precursor metabolites were performed under conditions of sodium depletion and ACTH stimulation. Plasma renin concentration was elevated in both patients, and stimulated plasma renin activity was low in one and normal in the other. Fractionation of plasma extracts demonstrated the presence of "big renin," a relatively inactive precursor of renin. Metabolites of aldosterone precursors were increased, suggesting deficient 18-hydroxylase in one patient and dehydrogenase in the other. The results suggest that hypoaldosteronism in diabetic patients may result from combined defects in both renin and aldosterone biosynthesis.

Adrenal Cortex↗
PubMed1976

Plasma renin activity and hypertension in diabetes mellitus.

Plasma renin activity (PRA) was determined in 48 patients with diabetes mellitus in sodium balance on a 10-20 mEq. Na diet. Nine were normotensive (group I), 11 11 were hypertensive without diabetic nephropathy (group III). Results were compared with those in 16 normal subjects and 49 nondiabetic patients with essential hypertension in similar Na balance. Mean supine PRA did not differ significantly among groups I and II, normal subjects, and patients with essential hypertension. Group III diabetics had a supine PRA of 2.4 +/- 0.4 ng./ml./hr. (x +/- S.E.M.), significantly lower than the other diabetic groups (P less than 0.005) and normal subjects (P less than 0.05). Upright PRA was 12.8 +/- 2.2 in group I diabetics, similar to that in normal subjects (13.3 +/- 2.3), and 8.1 +/- 1.4 in group II diabetics, similar to that in essential hypertensives (6.8 +/- 0.8). In group III diabetics, upright PRA was 4.0 +/- 0.5, significantly lower than that in any other group. These results suggest that (1) PRA is normal in normotensive diabetics, (2) upright PRA in diabetics with hypertension but no nephropathy is similar to that in essential hypertension, and (3) patients with diabetes, hypertension, and nephropathy have "low renin hypertension," explaining the virtual absence of malignant hypertension in this group. Although the major mechanism for this low PRA may be volume expansion, indicating the need for potent diuretics, other mechanisms include hyalinization of the afferent arteriole, decreased cathecholamine stimulation of renin release, and inadequate conversion of prorenin to renin.

Adult↗
PubMed1976

Vascular reactivity to angiotensin II and to norepinephrine in diabetic subjects.

Vascular responsiveness to infused angiotensin II and to norepinephrine was determined in 14 normal subjects and two groups of diabetic subjects, 16 with no clinically detectable diabetic complications and 14 with diabetic retinopathy but no clinical evidence of nephropathy. All were maintained on a 100-mEq. -Na- 100-mEq. -K diet. Serum electrolytes, 24-hour urinary sodium, creatinine clearance, and plasma renin activity did not differ significantly among the groups. Group mean baseline diastolic pressure in those with retinopathy was higher than in normal subjects but no significantly different from that of uncomplicated diabetics. The pressor dose of angiotensin II (ng./kg./min. to increase diastolic blood pressure 20 mm. Hg) for each group respectively was 11.5 +/-0.9, 12.9+/- 1.3, and 8.3 +/- 1.3, and the slope of the dose-response curve (mm. Hg rise in blood pressure resulting from the infusion of 1 ng./kg./min. following the initial increment in blood pressure) was 2.0 +/-0.2, 1.6+/-0.2, 3.3+/- 0.6. For norepinephrine, the pressor doses were 163 +/- 24, 212+/-21, and123 +/- 11 and slopes were 0.17 +/- 0.03, 0.13 +/- 0.02, and 0.20 +/-0.02. Neither diabetic group differed significantly from normal subjects. Diabetics with retinopathy were more sensitive to angiotensin II, pressor dose (P less than 0.059) and slope (P less than 0.02), and to norepinephrine, pressor dose (P less than 0.006) and slope (P =0.05) than those without complications. These data suggest that vascular reactivity is enhanced in diabetics with retinopathy.

Angiotensin II↗
PubMed1976

Renin-angiotensin-aldosterone system in diabetes mellitus.

The renin-angiotensin-aldosterone system appears to function normally in uncomplicated diabetes mellitus. Alterations in this system, however, have been observed in several of the microvascular and electrolyte complications associated with this disease. Plasma renin activity (PRA) and aldosterone are decreased in diabetic with nephropathy and hypertension, in those with neuropathy including orthostatic hypotension, and in those with hypoaldosteronism. PRA is low in rats with uncontrolled, nonketotic diabetes, and pressor responsiveness to angiotension II is increased in patients with diabetic retinopathy. Potential mechanisms responsible for the decreased PRA include plasma volume expansion, hyalin destruction of the juxtaglomerular cells, defective synthesis of renin, and inadequate catecholamine stimulation of renin, and inadequant cathecholamine stimulation of renin release. In diabetic ketoacidosis, PRA and aldosterone are stimulated secondary to the associated dehydration with hypovolemia. This report reviews the current status of the function of the renin-angiotensin-aldosterone system in diabetes mellitus and proposes a possible role for the altered function of this system in the pathophysiology of several diabetic complications.

Aldosterone↗
PubMed1975

Plasma renin activity and blood volume in uncontrolled diabetes. Ketoacidosis, a state of secondary aldosteronism.

The renin-angiotensin-aldosterone system was evaluated in two types of uncontrolled diabetes: a) diabetic ketoacidosis, and b) nonketotic hyperglycemia. In thirteen patients with ketoacidosis, mean plasma renin activity (PRA) was 58 plus or minus 12 (S.E.M.) ng. per milliliter per hour and in four patients, plasma aldosterone was 82 plus or minus 17 ng. per 100 ml. Corresponding values for upright salt-depleted subjects were 13 plus or minus 2 and 62 plus or minus 8. In eleven diabetics with nonketotic hyperglycemia (mean glucose 318 plus or minus 19 mg. per cent), mean blood volume was 4,660 ml. and PRA 2.1 plus or minus .7. After control of the diabetes (mean glucose 129 plus or minus 13) blood volume was 4,553 ml. and PRA 3.3 plus or minus 1 (NS). The results suggest that: 1) diabetic ketoacidosis is a state of severe secondary aldosteronism, 2) no significant change in blood volume or PRA occurs during short periods of hyperglycemia, and 3) insulin is not necessary for renin release.

Adult↗