Diabetes mellitus, the Renin-Angiotensin System, and Angiotensin-Converting Enzyme Inhibition

Björck, S; Aurell, Mattias

doi:10.1159/000186029

Cited by 17 publications

(5 citation statements)

References 78 publications

(122 reference statements)

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“…Plasma angiotensin II levels have been described as elevated or reduced in different studies of experimental diabetes [7,17]. In diabetic patients, elevated angiotensin II levels [20,21,48] may be lowered by improved glycaemic control, however, Ferris et al [49] measured a decrease in plasma angiotensin II in patients with neuropathy.…”

Section: Discussionmentioning

confidence: 99%

“…In diabetic patients, elevated angiotensin II levels [20,21,48] may be lowered by improved glycaemic control, however, Ferris et al [49] measured a decrease in plasma angiotensin II in patients with neuropathy. Furthermore, increased sensitivity to angiotensin II has been noted in both diabetic rats [50] and patients [17]. Despite this, receptor density in different tissues may be reduced [48,51,52].…”

Section: Discussionmentioning

confidence: 99%

“…Changes in the renin-angiotensin system could contribute to the vascular abnormalities of diabetes [7]. While there is some disagreement in the literature, increased plasma renin activity and elevated levels of angiotensin converting enzyme and angiotensin II have been reported [7,[17][18][19][20][21]. Such alterations may be relevant to the development of early neuropathic changes because treatment with the angiotensin-converting enzyme inhibitor, lisinopril, prevented the development of motor and sensory nerve dysfunction in streptozotocin-diabetic rats [22].…”

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confidence: 99%

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Angiotensin II receptor blockade improves nerve function, modulates nerve blood flow and stimulates endoneurial angiogenesis in streptozotocin-diabetic ratsand nerve function

et al. 1993

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We examined the effect of the angiotensin II receptor blocker, ZD 8731, on nerve function, capillary density, and blood flow in streptozotocin-diabetic rats. Deficits in sciatic motor and saphenous sensory nerve conduction velocity of 21% and 15%, respectively, were observed after 1 month of diabetes mellitus (p < 0.001). These were completely ameliorated by a further month of ZD 8731 treatment (p < 0.001). Treatment of non-diabetic rats for 1 month with ZD 8731 had no effect on motor or sensory conduction velocity. Sciatic nerve capillary density was not significantly affected by 1- or 2-month untreated diabetes, however, there was a 15% increase in density with ZD 8731 treatment (p < 0.001). Treatment of non-diabetic rats for 1 month had no effect on capillary density. Diabetes prolonged the time taken for 80% conduction failure by 19% (p < 0.05) and 49% (p < 0.001) for 1 and 2 months of diabetes, respectively, when sciatic nerve was exposed to hypoxia in vitro. ZD 8731 treatment during the second month of diabetes limited the prolongation to 22%, not significantly different from 1 month of untreated diabetes but less than for the 2-month diabetic group (p < 0.001). Concentrations of sciatic nerve polyol pathway metabolites were elevated six-fold and myo-inositol was reduced 40% by diabetes; ZD 8731 treatment was without effect. Acute experiments examined the effect of ZD 8731 on sciatic nerve blood flow using laser-Doppler flowmetry. In non-diabetic rats, blood flow changes followed the dose-dependent reductions in systemic arterial pressure and there were no significant variations in sciatic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Angiotensin II receptor blockade improves nerve function, modulates nerve blood flow and stimulates endoneurial angiogenesis in streptozotocin-diabetic ratsand nerve function

et al. 1993

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“…The streptozotocin diabetic rat is a useful model for studies of renal function in insulin-dependent diabetes mellitus, since both glomerular hypertrophy and increased G F R [ 131 are found in moderately hyperglycaemic diabetic animals. Micropuncture studies in the diabetic rats have demonstrated increases in both nephron perfusion and filtration as well as intraglomerular pressure [14].…”

Section: Discussionmentioning

confidence: 99%

Angiotensin converting enzyme activity in the serum, lung and kidney of diabetic rats

Erman

Dyk

Chen-Gal

et al. 1993

Eur J Clin Investigation

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Diabetes Mellitus in its early stages, is associated with kidney enlargement and increased glomerular filtration rate in humans and in rats. The present study was designed to clarify the direct effect of diabetes on serum and tissue angiotensin converting enzyme (ACE) activity in streptozotocin-induced diabetic rats. Serum ACE activity, as determined using a radiometric assay, was significantly increased in the diabetic rats (n = 15) 14 days after induction of diabetes (670 +/- 31 vs. 506 +/- 14 nmol ml-1 min-1). Lung ACE activity, but not renal, was significantly elevated at 7 and 14 days by 29 and 46%, respectively. Plasma renin activity in the diabetic rats was decreased at 7 and 14 days by 41 and 78%, respectively. Incubations of lung slices in the presence of glucose at different concentrations did not affect in-vitro release of the enzyme. Administration of insulin (8 units kg-1) to diabetic rats (n = 6) on the 4th day for 11 days reduced ACE activity to values below control. Thus, serum and lung ACE activity is increased in the diabetic rat and reduced upon insulin treatment.

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“…The renin-angiotensin system is not only implicated in systemic blood pressure regulation, but it also has a signif icant role in regulating kidney microcirculation [3], An giotensin II (A II) has multiple renal actions, including the following: regulation and redistribution of renal blood (low; differential vasoconstrictor effects on the efferent and afferent arterioles of the glomerulus; contraction of the mesangium; regulation of vasa recta blood flow, with effects on renal concentrating ability; suppression of renin synthesis and release, and an influence on sodium trans port in the proximal tubule [4]. Studies have demon strated that the inhibition of intrarenal generation of A II by angiotensin-converting enzyme inhibitors (ACEI) may preferentially dilate the efferent glomerular arteriole and lead to a fall in intraglomerular pressure.…”

Section: Introductionmentioning

confidence: 99%

Scintigraphic Evaluation of Functional Renal Reserve Using Angiotensin-Converting Enzyme Inhibition in Patients with Type II Diabetes Mellitus

Erbaş

Erbaş²,

Akalın³

et al. 1993

Am J Nephrol

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Acute effects of 20 mg oral enalapril (E), and angiotensin-converting enzyme inhibitor, on renal function and the renin-angiotensin-aldosterone system were investigated in 13 patients with type II diabetes mellitus (8 female, 5 male) and 10 hypertensive controls using a radionuclide method. Plasma glucose control was evaluated with fructosamine (F) determinations. After intravenous administration of 370 MBq ^99mTc-DTPA, sequential images were recorded. Glomerular filtration rate (GFR), perfusion index (PI), time to maximum activity and reno index values of the kidneys were calculated. Two days later, renal scintigraphy was repeated after oral administration of E. Plasma levels of renin, angiotensin II and aldosterone were analyzed using RIA. Basal GFR values (mean: 92.6 ml/min) correlated with F (r = 0.364; p < 0.05). In the diabetic group, 5 patients had a decrease in GFR and an increase in PI after oral E. The mean percent change of GFR was 12 ± 32 for patients and 20 ± 12 for controls, respectively. Percent change of GFR had a slightly negative correlation with F values (r = -0.51; p < 0.05) and with PI (r = -0.65; p < 0.001). The patients with good metabolic control had an increase in GFR and a decrease in PI indicating an increase in renal blood flow and glomerular filtration. In patients with proteinuria and poorly controlled diabetes, in response to E-induced efferent arteriolar dilation, there is a decrease in GFR and an increase in PI which indicates a fall in filtration and renal blood flow. This glomerular hemodynamic pathology precedes morphological changes due to diabetes.

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Diabetes mellitus, the Renin-Angiotensin System, and Angiotensin-Converting Enzyme Inhibition

Cited by 17 publications

References 78 publications

Angiotensin II receptor blockade improves nerve function, modulates nerve blood flow and stimulates endoneurial angiogenesis in streptozotocin-diabetic ratsand nerve function

Angiotensin II receptor blockade improves nerve function, modulates nerve blood flow and stimulates endoneurial angiogenesis in streptozotocin-diabetic ratsand nerve function

Angiotensin converting enzyme activity in the serum, lung and kidney of diabetic rats

Scintigraphic Evaluation of Functional Renal Reserve Using Angiotensin-Converting Enzyme Inhibition in Patients with Type II Diabetes Mellitus

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