Impaired renal responsiveness to human atrial natriuretic peptide (hANP) in normotensive patients with type 1 diabetes mellitus

Jungmann, E.; Walter-Schräder, M.-C.; Haak, Thomas; Fassbinder, W; Wambach, G.; Althoff, P. H.; Schöffling, Κ.

doi:10.1007/bf01736521

Cited by 15 publications

(12 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(1989) found significant decreases in low density lipoproteins in nondiabetic hypertensive patients but not in diabetic patients with similarly elevated high blood pressure. Jungmann et al (1988) reported an impairment of the renal action of human atrial natriuretic peptide in 100M patients with hyperglycaemia, but not in similar patients with well controlled blood glucose concentrations (Jungmann et at. 1989).…”

Section: Pharmacodynamicsmentioning

confidence: 96%

The Effects of Diabetes Mellitus on Pharmacokinetics and Pharmacodynamics in Humans

Gwilt

Nahhas

Tracewell

1991

Clinical Pharmacokinetics

142

View full text Add to dashboard Cite

The article reviews the effect of diabetes on the pharmacokinetics and pharmacodynamics of drugs in humans. For most drugs which cross the gastrointestinal wall by passive diffusion, oral absorption is unlikely to be affected by diabetes, although a delay in the absorption of tolazamide and a decrease in the extent of absorption of ampicillin have been reported. Subcutaneous absorption of insulin is more rapid in diabetic patients, whereas the intramuscular absorption of several drugs is slower. The binding of a number of drugs in the blood is reduced in diabetes, which may be due to glycosylation of plasma proteins or displacement by plasma free fatty acids, the level of which is increased in diabetic patients. Plasma concentrations of albumin and alpha 1-acid glycoprotein do not appear to be changed by the disease. The distribution of drugs with little or no binding in the blood is generally not altered, although the volume of distribution of phenazone (antipyrine) is reduced by 20% in insulin-dependent diabetes mellitus (IDDM). In contrast to animal studies, the metabolic clearance of most drugs in humans appears to be unaffected or slightly reduced by the disease. The presence of fatty liver in non-insulin-dependent diabetes mellitus (NIDDM) may contribute to a reduced hepatic clearance, whereas decreased binding in the blood may cause an increase in clearance. The effect of diabetes on hepatic blood flow in humans appears to be unknown. Diabetes affects kidney function in a significant number of diabetic patients. During the first 10 years after the onset of the disease, glomerular filtration is elevated in these patients. Thus, the renal clearance of a number of antibiotics has been shown to be increased in diabetic children. As the disease progresses, renal function is impaired and glomerular function declines from the initial elevated state. In diabetic adults the renal clearance of drugs either is comparable with that found in nondiabetic individuals or is reduced. A limited number of studies have been conducted comparing the dose-response of cardiovascular drugs in diabetic patients with that in nondiabetic controls. Decreased, increased and unchanged responses have been reported. It is apparent that in some cases an altered response may be observed for a drug when administered to a diabetic patient compared with a similar nondiabetic individual. At the present time, it is not possible to ascertain whether these studies reflect true pharmacodynamic changes or merely alterations in pharmacokinetics.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

Section: Pharmacodynamicsmentioning

confidence: 96%

The Effects of Diabetes Mellitus on Pharmacokinetics and Pharmacodynamics in Humans

Gwilt

Nahhas

Tracewell

1991

Clinical Pharmacokinetics

142

View full text Add to dashboard Cite

show abstract

“…Water immersion as well as an intravenous sodium load, both methods used to induce increments in endogenous ANF concentrations, exerted an impaired diuretic and natriuretic response in diabetic patients compared with control subjects (7,8), and similar results were obtained after exogenous ANF administration (10,11).…”

mentioning

confidence: 58%

“…Consequently, the BP response to ANF infusion cannot be considered to be a representative parameter for the direct vascular effects of ANF. Therefore, none of the previous observations on the systemic effects of ANF (10,11,17) can solve the question whether the direct vascular effect of ANF is changed in diabetes. These observations convincingly show for the first time that uncomplicated human IDDM is associated with an impaired vasodilator response to the endogenous hormone ANF.…”

Section: Discussionmentioning

confidence: 96%

“…At this lowest rate of 0.001 |xg of ANF • min~1 • 100 ml" 1 of forearm tissue, regional plasma ANF concentrations have been reported to be in the upper normal range (2). Therefore, the fact that the difference between diabetic In IDDM, Jungmann et al (10) showed a reduction in the natriuretic response to ANF infusion without differences in the response of BP, suggesting a normal vascular responsiveness to ANF. In contrast, other investigators showed an impaired fall in BP or in peripheral vascular resistance in diabetic patients compared with control subjects after the intravenous administration of ANF (11,17).…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Impaired Vasodilator Response to Atrial Natriuretic Factor in IDDM

Smits

Hersbach²,

Jansen³

et al. 1993

Diabetes

View full text Add to dashboard Cite

Diabetes mellitus has been associated with both elevated plasma concentrations of the natriuretic and vasorelaxant hormone atrial natriuretic factor and with a reduced natriuretic response to this hormone. We now hypothesize that the vasodilator response to atrial natriuretic factor is attenuated in IDDM. Forearm vasodilator responses to the infusion of six increasing dosages of atrial natriuretic factor into the brachial artery were registered by venous occlusion strain gauge plethysmography in 10 patients with uncomplicated IDDM and in 10 age-, sex-, and weight-matched control subjects. Baseline levels of blood pressure, forearm blood flow, and plasma concentrations of atrial natriuretic factor were not different between control subjects and patients with diabetes. In control subjects, atrial natriuretic factor induced a percentage fall in the forearm vascular resistance of -29 +/- 5% at the lowest to -72 +/- 4% at the highest infusion rate. In patients with diabetes this fall was significantly attenuated, measuring -2 +/- 7 and -45 +/- 4%, respectively, (P< 0.001 vs. control subjects). During infusion of atrial natriuretic factor into the brachial artery, the calculated regional production of cGMP (second messenger of atrial natriuretic factor) increased from 1.2 +/- 1.1 to 22.8 +/- 4.8 pmol.min-1 x 100 ml-1 in the control subjects, whereas hardly any change occurred in the patients with diabetes (from -2.1 +/- 1.2 to 2.9 +/- 4.7 pmol.min-1 x 100 ml-1). Furthermore, both control and diabetic subjects demonstrated an equal forearm vasodilator response to increasing infusion rates of the control vasodilator sodium nitroprusside. We conclude that uncomplicated IDDM is associated with a specific reduction in the vascular responsiveness to atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

“…Diabetes is another condition characterized by a high plasma A N P and reduced responsiveness of the kidney to exogenous A N P [133][134][135]. Studies showed that cardiac A N P synthesis is augmented in streptozotocin-induced rats, which could be reversed with insulin therapy [136], Increase in plasma A N P is felt to be secondary to the volume expansion induced by hyperglycemia [137].…”

Section: Diabetes Mellitusmentioning

confidence: 99%