Inhibition of Nitric Oxide Synthesis in Forearm Vasculature of Insulin-Dependent Diabetic Patients: Blunted Vasoconstriction in Patients with Microalbuminuria

1993 ◽  
Vol 85 (6) ◽  
pp. 687-693 ◽  
Author(s):  
T. G. Elliott ◽  
J. R. Cockcroft ◽  
P.-H. Groop ◽  
G. C. Viberti ◽  
J. M. Ritter
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Healthy Subjects ◽  
Diabetic Patients ◽  
Control Subjects ◽  
Relaxing Factor ◽  
Healthy Control ◽  
Insulin Dependent ◽  
Endothelium Derived Relaxing Factor ◽  
Insulin Dependent Diabetic

1. Microalbuminuria is a risk factor for cardiovascular disease in patients with insulin-dependent diabetes mellitus, and may be a marker of microvascular dysfunction including endothelial damage. The purpose of this study was to determine whether vasoconstrictor responses to NG-monomethyl-L-arginine, an inhibitor of endothelium-derived relaxing factor/nitric oxide biosynthesis, differ between healthy subjects and insulin-dependent patients with or without microalbuminuria. 2. Twenty-eight insulin-dependent diabetic patients (14 with normal albumin excretion, 14 with microalbuminuria) were studied under euglycaemic conditions, together with 14 healthy control subjects. Forearm vascular responses to brachial artery infusions of NG-monomethyl-L-arginine, sodium nitroprusside (an endothelium-independent nitrovasodilator) and carbachol (an endothelium-dependent vasodilator) were determined by strain gauge plethysmography. 3. Basal blood flow and vasodilator responses were similar in each group. NG-Monomethyl-L-arginine reduced blood flow by 41.3 + 2.3% (mean + SEM) in healthy control subjects, 34.0 + 3.4% in diabetic patients without microalbuminuria and 29.2 + 2.0% in diabetic patients with microalbuminuria. Diabetic patients differed from healthy subjects (P = 0.005), due to a difference between control subjects and microalbuminuric diabetic patients (P <0.001). NG-Monomethyl-L-arginine did not influence nitroprusside responses but reduced carbachol responses in control subjects and normoalbuminuric diabetic patients but not in microalbuminuric diabetic patients. 4. These results provide evidence of abnormal endothelium-derived relaxing factor/nitric oxide biosynthesis in insulin-dependent diabetic patients with microalbuminuria.

Cutaneous blood flow during a hypoglycaemic clamp in insulin-dependent diabetic patients and healthy subjects

1992 ◽  
Vol 82 (6) ◽  
pp. 615-618 ◽  
Author(s):  
J. Åman ◽  
C. Berne ◽  
U. Ewald ◽  
T. Tuvemo
Keyword(s):  
Blood Flow ◽  
Glucose Concentration ◽  
Healthy Subjects ◽  
Diabetic Patients ◽  
Cutaneous Blood Flow ◽  
Control Subjects ◽  
Cutaneous Vasodilatation ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
Cutaneous Blood

1. A marked cutaneous vasodilatation has been shown to occur in healthy subjects, but not in insulin-dependent diabetic patients, in response to hypoglycaemia induced by a rapid intravenous bolus injection of insulin. 2. In the present study cutaneous blood flow in response to a gradual decline in blood glucose concentration was investigated in eight young adult diabetic patients and in eight age- and sex-matched control subjects. After a hyperinsulinaemic euglycaemic clamp for 40 min, hypoglycaemia was induced (plasma glucose concentration 2 mmol/l) by a standardized stepwise reduction in the intravenous glucose infusion 3. Blood flow was measured by using a laser Doppler sensor and a cutaneous O2 electrode placed on the medial aspect of the forearm, and a laser Doppler sensor placed on the forehead. 4. No significant change in cutaneous blood flow occurred during euglycaemic hyperinsulinaemia. 5. In control subjects a marked increase in blood flow during hypoglycaemia was observed in the forearm by both methods. No corresponding change was observed in the forehead. 6. In the diabetic patients the increase in cutaneous blood flow was absent in both the forearm and forehead. 7. It is concluded that hypoglycaemia, but not hyperinsulinaemia, is associated with a regional cutaneous vasodilatation in healthy control subjects. This cutaneous vasodilatation is absent in diabetic patients.

scholarly journals Cerebral blood flow increases during insulin-induced hypoglycaemia in Type 1 (insulin-dependent) diabetic patients and control subjects

Diabetologia ◽  
1987 ◽  
Vol 30 (5) ◽  
pp. 305-309 ◽  
Author(s):  
H. A. W. Neil ◽  
E. A. M. Gale ◽  
S. J. C. Hamilton ◽  
I. Lopez-Espinoza ◽  
R. Kaura ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Diabetic Patients ◽  
Control Subjects ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
And Control

scholarly journals Skin Microcirculation of the Foot in Diabetic Neuropathy

1996 ◽  
Vol 91 (5) ◽  
pp. 559-565 ◽  
Author(s):  
Paetrick M. Netten ◽  
Hub Wollersheim ◽  
Theo Thien ◽  
Jos A. Lutterman
Keyword(s):  
Diabetic Neuropathy ◽  
Laser Doppler ◽  
Diabetic Patients ◽  
Shunt Flow ◽  
Laser Doppler Fluxmetry ◽  
Control Subjects ◽  
Healthy Control ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
And Control

1. In the feet of patients with diabetic neuropathy, total skin blood flow is increased due to an increased shunt flow. The question is, does this increased anastomotic shunt flow lead to either under- or overperfused nutritive capillaries. 2. To solve this question, skin microcirculation tests of the left big toe were performed in 20 healthy control subjects and in 40 insulin-dependent diabetic patients without macroangiopathy, 20 without and 20 with neuropathy. Skin temperature measurements and laser Doppler fluxmetry were performed to record mainly shunt flow and capillaroscopy to study nailfold capillary blood flow. 3. The insulin-dependent diabetic patients with neuropathy had a higher baseline skin temperature (mean ± SEM; 30.0 ± 0.6°C) and laser Doppler fluxmetry [26.2 ± 2.2 perfusion units (pu)] than patients without neuropathy (27.2 ± 0.8°C, P < 0.01; 16.1 ± 2.0 pu, P < 0.01) and healthy control subjects (27.9 ± 0.7°C, P < 0.05; 18.6 ± 2.8 pu, P < 0.05). Sympathetic stimulation (inspiratory gasp) resulted in a smaller laser Doppler fluxmetry decrease in the neuropathic patients (31.4 ± 4.6%) compared with non-neuropathic patients (48.2 ± 5.1%, P < 0.05) and control subjects (49.0 ± 3.8%, P < 0.05), while no difference between the three groups was seen in the laser Doppler fluxmetry decrease during a postural vasoconstriction test. The number of visible capillaries was highest in the neuropathic patients (10.2 ± 0.6/0.5 mm2), when compared with non-neuropathic patients (8.7 ± 1.2/0.5 mm2, P < 0.05) and control subjects (8.3 ± 0.3/0.5 mm2, P < 0.001). Capillary blood-cell velocity was significantly higher in the neuropathic patients (0.32 ± 0.05 mm/s) compared with non-neuropathic patients (0.23 ± 0.03 mm/s, P < 0.05) and control subjects (0.23 ± 0.02 mm/s, P < 0.01). 4. We conclude that there is an overperfused nutritive capillary circulation in the feet of patients with diabetic neuropathy. This is in contradiction to the capillary steal phenomenon and favours the hyperdynamic hypothesis to explain the decreased healing potential in diabetic neuropathic foot ulceration.

Decreased distensibility of resistance vessels of the skin in type 1 (insulin-dependent) diabetic patients with microangiopathy

1987 ◽  
Vol 72 (1) ◽  
pp. 123-130 ◽  
Author(s):  
J. Kastrup ◽  
T. Nørgaard ◽  
H.-H. Parving ◽  
N. A. Lassen
Keyword(s):  
Blood Flow ◽  
Inverse Correlation ◽  
Diabetic Patients ◽  
Resistance Vessels ◽  
Head Up Tilt ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
Type 1 Diabetic Patients ◽  
Term Type

1. The distensibility of the resistance vessels of the skin at the dorsum of the foot was determined in 11 long-term type 1 (insulin-dependent) diabetic patients with nephropathy and retinopathy, nine short-term type 1 diabetic patients without clinical microangiopathy and in nine healthy non-diabetic subjects. 2. Blood flow was measured by the local 133Xexenon washout technique in a vascular bed locally paralysed by the injection of histamine. Blood flow was measured before, during and after a 40 mmHg increase of the vascular transmural pressure, induced by head-up tilt. 3. The mean increase in blood flow during headup tilt was only 24% in diabetic subjects with and 48% in diabetic patients without clinical microangiopathy, compared with 79% in normal non-diabetic subjects (P < 0.0005 and P < 0.05, respectively). 4. An inverse correlation between microvascular distensibility and degree of hyalinosis of the terminal arterioles in biopsies from the skin was demonstrated (r = − 0.57, P < 0.001). 5. Our results suggest that terminal arteriolar hyalinosis reduces the microvascular distensibility and probably increases the minimal vascular resistance, thereby impeding hyperaemic responses.

Effect of Posture and Acute Glycaemic Control on the Excretion of Retinol-Binding Protein in Normoalbuminuric Insulin-Dependent Diabetic Patients

1993 ◽  
Vol 84 (4) ◽  
pp. 461-467 ◽  
Author(s):  
Carlo Catalano ◽  
Peter H. Winocour ◽  
Susan Gillespie ◽  
Ian Gibb ◽  
K. George M. M. Alberti
Keyword(s):  
Blood Glucose Concentration ◽  
Excretion Rate ◽  
Binding Protein ◽  
Insulin Dependent Diabetes ◽  
Retinol Binding Protein ◽  
Diabetic Patients ◽  
Control Subjects ◽  
Protein Excretion ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic

1. It has been suggested that tubular damage may precede gomerular damage at the onset of diabetic nephropathy. This may be reflected by increased urinary excretion of low-molecular-mass proteins, such as retinol-binding protein. 2. We have measured the urinary excretion rate of retinol-binding protein overnight, during orthostasis and during a hyperinsulinaemic euglycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 34 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 10 normal control subjects. Normal control subjects were not clamped. A further four normoalbuminuric insulin-dependent diabetic patients were rendered euglycaemic without a water load. 3. Overnight retinol-binding protein excretion rate was 58 (16-157) [median(range)] ng/min in patients with insulin-dependent diabetes and 32 (15-72) ng/min in control subjects (P < 0.01). The excretion rate did not change during orthostasis [patients with insulin-dependent diabetes, 67 (3-173) ng/min; control subjects, 23 (5-78) ng/min]. During the euglycaemic clamp retinol-binding protein excretion rate increased to 383 (78-4897) ng/min in patients with insulin-dependent diabetes (P < 0.01). An average increment in retinol-binding protein excretion rate of greater than 4000% was noted after acute euglycaemia in those patients with insulin-dependent diabetes who were not water-loaded. 4. In insulin-dependent diabetes, both overnight and orthostatic retinal-binding protein excretion was not correlated with fasting blood glucose concentration, HbA1, fructosamine or duration of diabetes. The absolute and incremental excretion rates of retinol-binding protein during the clamp were, however, correlated with both fasting blood glucose concentration and glucose excretion rate (rs = 0.41-0.48, P < 0.01). 5. The study demonstrates that retinol-binding protein excretion is increased in insulin-dependent diabetes in the absence of microalbuminuria and that this increase in retinol-binding protein excretion is particularly pronounced after acute euglycaemia. Acute tubular dysfunction related to acute changes in glucose control appears to be the most likely explanation, but established tubular damage could also be implicated. Postural variation in retinol-binding protein excretion was not detected.

Glucocorticoid-induced renal vasodilatation is mediated by a direct renal action involving nitric oxide

1997 ◽  
Vol 273 (6) ◽  
pp. R1972-R1979 ◽  
Author(s):  
R. De Matteo ◽  
C. N. May
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Plasma Cortisol ◽  
Filtration Rate ◽  
Systemic Effects ◽  
Renal Vasculature ◽  
Relaxing Factor ◽  
Renal Action ◽  
Endothelium Derived Relaxing Factor ◽  
Conscious Sheep

Glucocorticoids increase renal blood flow (RBF) and glomerular filtration rate, but the mechanisms are unclear. We investigated whether the cortisol-induced increment in RBF is a direct renal action or secondary to its systemic effects and whether nitric oxide (NO) plays a role in this response. In conscious sheep, cortisol infused intravenously (5.0 mg/h) or into the renal artery (1.3 mg/h) for 5 h increased RBF by 66 ± 8 and 53 ± 11 ml/min, respectively. Plasma glucose was increased by intravenous cortisol (0.4 ± 0.1 mmol/l) but not by intrarenal cortisol. Renal vein plasma cortisol levels were similar at the end of each infusion (193 ± 31 intravenously; 151 ± 25 nmol/l intrarenal), but systemic levels were different (277 ± 31 intravenous; 69 ± 10 nmol/l intrarenal). Inhibition of NO synthesis by N ω-nitro-l-arginine infused intravenously (10 mg/kg followed by 5 mg ⋅ kg−1 ⋅ h−1) or intrarenally (2 mg ⋅ kg−1 ⋅ h−1) significantly reduced the cortisol-induced renal vasodilatation. In contrast, constriction of the renal vasculature with intrarenal angiotensin (0.3 μg/h) did not prevent the cortisol-induced renal vasodilatation. These findings demonstrate that cortisol acts directly on the kidney to cause renal vasodilatation and to increase RBF and suggest that this response involves the endothelium-derived relaxing factor NO.

Saliva in non-insulin-dependent diabetic patients and control subjects

1998 ◽  
Vol 86 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Jukka H Meurman ◽  
Hanna-Leena Collin ◽  
Leo Niskanen ◽  
Jari Töyry ◽  
Pekka Alakuijala ◽  
...  
Keyword(s):  
Diabetic Patients ◽  
Control Subjects ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic ◽  
And Control
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