atrial-natriuretic-factor and Diabetic-Neuropathies

The renin angiotensin system (RAS) is a peptide hormone system that plays an important role in the pathophysiology of various diseases, including congestive heart failure, hypertension, myocardial infarction, and diabetic nephropathy. This has led researchers to focus extensively on this system, leading to the discovery of various peptides, peptidases, receptors and signal transduction mechanisms intrinsic to the RAS. Angiotensinogen (AGT), angiotensin (Ang) II, Ang III, Ang IV, and Ang-(1-7) are the main biologically active peptides of RAS. However, most of the available studies have focused on Ang II as the likely key peptide from the RAS that directly and indirectly regulates physiological functions leading to pathological conditions. However, data from recent studies suggest that Ang III may produce physiologically relevant effects that are similar to those produced by Ang II. Hence, this review focuses on Ang III and the myriad of physiological effects that it produces in the body.

Topics: Angiotensin III; Animals; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cardiovascular Diseases; Diabetic Neuropathies; Humans; Rats; Renin-Angiotensin System; Signal Transduction; Sodium; Thirst; Vasopressins

This study sought to determine if the severity of autonomic perturbations in patients with heart failure are affected by the presence of diabetes. Decreased HRV is frequent in diabetic patients free of clinically apparent heart disease and has been invoked as a risk factor for sudden cardiac death. However, reduced HRV is also commonly present in patients with left ventricular dysfunction. The effect of diabetes on autonomic dysfunction in this setting is not known. Holter ECGs from 69 diabetic patients and 85 nondiabetic control subjects with heart failure were analyzed. The severity of autonomic dysfunction was assessed using 24-hour time- and frequency-domain HRV analysis. Prognostically important time- and frequency-domain HRV measures (SDNN, SDANN5, total power, and ultra-low frequency power) were not different between the two groups. Time- and frequency-domain parameters modulated by parasympathetic tone (pNN50, RMSSD, and HF power) were depressed to a similar degree in the diabetic and the nondiabetic groups. The low frequency power was significantly lower in diabetic patients (5.8 +/- 0.7 vs 5.3 +/- 1.0, P = 0.02). The ratio of low to high frequency power was substantially lower in the diabetic group (2.2 +/- 0.2 vs 1.4 +/- 0.2, P < 0.0001). These differences were more apparent in insulin-treated diabetics. In the presence of heart failure, HRV parameters that are most predictive of adverse outcome are similar in diabetic and nondiabetic patients. Furthermore, during increased sympathetic stimulation in the setting of heart failure, diabetes does not worsen parasympathetic withdrawal but may mitigate sympathetic activation.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dobutamine; Electrocardiography, Ambulatory; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Signal Processing, Computer-Assisted

The objective of this study was to determine the role of atrial natriuretic peptide (ANP) in autonomic neuropathy and to learn the effect of saline solution infusion on ANP. Twenty one subjects were distributed in three groups: 1) control group, 2) diabetic patients with autonomic neuropathy, and 3) diabetic patients without autonomic neuropathy. The levels of ANP, renin, aldosterone and cortisol were determined at baseline and 30, 60, and 75 min after saline infusion. At baseline ANP was lower in diabetic patients with autonomic neuropathy (32.9 +/- 13) than control group (34 +/- 15). ANP increased statistically significantly at 30 min after solution administration in control group (60 +/- 35, F = 4, p < 0.05), but it did not change in diabetic patients (Group II: 34.3 +/- 9.3 and Group III 34.6 +/- 10.7). Sixty and 75 min after saline infusion ANP returned to basal levels in control group, but they did not change in diabetic patients. A delayed response of renin, aldosterone and cortisol to saline solution administration was observed in diabetic patients. There was no correlation between ANP levels and alteration of autonomic tests. It is concluded that independent of autonomic neuropathy, the levels of ANP did not increase with saline infusion in diabetic patients.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Hydrocortisone; Middle Aged; Plasma Volume; Renin; Sodium Chloride

We compared plasma ANF concentration in 5 diabetic-uremics with combined sympathetic-parasympathetic dysfunction with that in 9 uremic patients without autonomic impairment. Symptomatic dialysis hypotension was a major clinical problem in all diabetic-uremics. In the volume-expanded state, ANF was almost twice as high (p less than 0.025) in diabetic-uremics than in control uremics (152 +/- 29 vs 84 +/- 10 pg/ml) in the face of similar right atrial pressure (14 +/- 3 vs 12 +/- 1 cm H2O). After isolated ultrafiltration, ANF fell significantly in both groups remaining slightly (NS) higher in diabetic-uremics. The slope of the relationship between ANF and right atrial pressure was significantly (p less than 0.01) steeper in diabetic-uremics than in control uremics. The data indicate that autonomic failure amplifies the effect of atrial stretching on plasma ANF in diabetic-uremics on chronic hemodialysis treatment.

Topics: Adult; Atrial Natriuretic Factor; Autonomic Nervous System Diseases; Blood Pressure; Diabetic Nephropathies; Diabetic Neuropathies; Humans; Male; Middle Aged; Renal Dialysis; Uremia

To investigate the influence of postural changes on plasma renin activity (PRA), plasma levels of human atrial natriuretic peptide (hANP) and on aldosterone in diabetes mellitus and autonomic neuropathy, ten patients with diabetes mellitus and autonomic neuropathy and ten patients with diabetes mellitus but without autonomic neuropathy were studied. Ten healthy subjects served as controls. Patients and controls were in supine position for 60 minutes, then changed posture sequentially to sitting (90 minutes) and to upright position (15 minutes). In controls, PRA was increased upon sitting and in the upright position, while hANP was decreased. Patients with autonomic neuropathy differed from controls in impaired renin stimulation, whereas in patients without autonomic neuropathy PRA responses to postural changes were only slightly decreased. In both groups of patients, the normal hANP responsiveness to postural changes was lacking. There were no differences in aldosterone levels between patients and controls. In patients with high basal hANP levels due to elevated systolic blood pressure renin responses to postural changes were decreased in comparison to those patients with low basal hANP levels. Thus, in patients with diabetes mellitus increased hANP levels which are not decreased in response to upright standing may contribute to the development of hyporeninism and its sequelae.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Autonomic Nervous System Diseases; Diabetic Neuropathies; Humans; Middle Aged; Posture; Renin; Renin-Angiotensin System

The effect of postural changes on plasma atrial natriuretic factor (ANF) levels was investigated in 16 diabetic hypertensives (eight with and eight without mild autonomic neuropathy) and in 10 hypertensives. The presence of renal damage or secondary hypertension was excluded. All diabetic patients were in good metabolic control. In upright position, the mean levels of plasma ANF were of 23.1 +/- 7.6 pg/mL in neuropathic diabetic hypertensives, 24.2 +/- 8.3 pg/mL in diabetic hypertensives, and 21.6 +/- 6.7 in essential hypertensives. Percentage decrease observed after the assumption of supine position was 47 +/- 18, 50 +/- 10, and 46 +/- 13, respectively. No significant difference was found between hypertensives and diabetic hypertensives, even in the presence of mild autonomic neuropathy. Plasma ANF response to postural changes was similar in all groups.

Topics: Adult; Angiotensin II; Atrial Natriuretic Factor; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Hypertension; Male; Middle Aged; Posture; Renin

In order to determine the effect of diabetic autonomic neuropathy (DAN) on the atrial natriuretic peptide (ANP) response to dynamic stimuli, we studied the ANP response to 60 degrees head-up and 60 degrees leg-up tilt in diabetic subjects with (DAN + ve, n = 8) and without (DAN - ve, n = 8) evidence of autonomic neuropathy and seven matched non-diabetic controls. Mean baseline plasma ANP concentrations were similar in all three groups. Head-up tilt was associated with a fall in plasma ANP in all seven healthy controls (21.8 (16.8-30.7) to 16.8 (7.1-29.1), P = 0.06, mean (range)), seven of the eight DAN - ve (16.9 (6.5-33.7) to 8.5 (3.0-21.1), P = 0.015) and all eight DAN + ve subjects (27.3 (8.5-101.5) to 15.4 (1.0-67.6), P = 0.044). Leg-up tilt caused a rise in plasma ANP in six of the seven healthy controls (17.6 (7.5-27.9) to 22.4 (15.2-48.1), P = 0.041), six of the eight DAN - ve (12.5 (7.8-27.8) to 15.5 (7.3-31.3), P = 0.054) and seven of the eight DAN + ve subjects (18.2 (2.8-55.1) to 25.1 (4.5-92.8), P = 0.013). There was no significant difference in the fall in plasma ANP during head-up tilt or in the rise in plasma ANP during leg-up tilt between the three groups. We conclude that the regulation of ANP secretion is normal in diabetes mellitus, and is unaffected by the presence of autonomic neuropathy.

Topics: Adult; Atrial Natriuretic Factor; Autonomic Nervous System; Blood Glucose; Blood Volume; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Hematocrit; Humans; Male; Middle Aged; Osmolar Concentration

The hormonal and renal response to volume expansion, produced by water immersion for 4 h, was studied in 14 insulin-dependent diabetic subjects (seven without complications, seven with autonomic neuropathy) and in 14 age-and-sex-matched normal control subjects. The diabetic subjects showed an impaired natriuretic response to volume expansion (total amount of sodium excreted 21 mmol compared to 39 mmol in normals, P less than 0.01) but the response did not differ in those with and without autonomic neuropathy. There was no significant difference in the suppression of plasma renin or aldosterone during immersion in either group. Plasma catecholamines suppressed on immersion in all groups. Basal values were lowest in the group with autonomic involvement. Atrial natriuretic peptide levels showed a twofold rise (from 4.8 to 9.6 pmol/l, P less than 0.01) on immersion. There was no significant difference in the levels of this hormone between diabetic patients and normal subjects or between those diabetics with and those without autonomic neuropathy. The present study confirms that diabetic subjects retain sodium avidly during volume expansion. This enhancement cannot be ascribed to any measurable difference in the levels of circulating hormones known to be involved in natriuresis and is not influenced by the presence of autonomic neuropathy.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Autonomic Nervous System Diseases; Blood Volume; Catecholamines; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Diuresis; Female; Hormones; Humans; Immersion; Male; Middle Aged; Natriuresis; Renin

In order to determine whether atrial natriuretic hormone (ANH) secretion is altered in diabetic patients with autonomic neuropathy, plasma immunoreactive ANH (IR-ANH) levels were measured in 23 patients with insulin-dependent diabetes mellitus, 12 of whom had definite cardiac autonomic neuropathy determined by noninvasive maneuvers. Levels were also measured in 31 healthy control subjects. Whereas only one of the 11 diabetics without cardiac autonomic neuropathy had elevated IR-ANH levels, four of the 12 diabetics with cardiac autonomic neuropathy had elevated IR-ANH levels (P = 0.03 compared to control subjects). 24-h urinary sodium excetion was not different among the groups. There was no significant correlation between IR-ANH levels and diabetes control and any of the parameters of autonomic nervous system activity nor between IR-ANH levels and plasma norepinephrine or epinephrine levels. Furthermore, no relationship was observed in the diabetic subjects between IR-ANH levels and left ventricular ejection fraction determined by radionuclide ventriculography. Thus, elevated IR-ANH levels occur with greater frequency in diabetic patients with autonomic neuropathy. These elevations do not appear to be due to alterations in dietary sodium intake or left ventricular dysfunction.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Epinephrine; Female; Heart Rate; Humans; Male; Norepinephrine; Pulse

We have investigated the influence of body fluid volume status on plasma levels of immunoreactive atrial natriuretic peptide (irANP) in eight uraemic patients on chronic haemodialysis, including two diabetics with severely impaired reflex control of the heart. IrANP was significantly higher in volume-expanded uraemic patients (36 +/- 16 pg/ml) than in a group of seven age and sex-matched normal subjects (14 +/- 2 pg/ml), and fell consistently, approaching the normal range after the removal of 2.0-4.3 litres of isotonic plasma ultrafiltrate (by isolated ultrafiltration). Plasma levels of the hormone were strictly related to right atrial pressure. The irANP response to ultrafiltration in the two diabetics was similar to that of the other uraemic patients. The results suggest that the elevated irANP levels found in volume-expanded uraemic patients depend largely on fluid overload per se. The preserved irANP response to ultrafiltration of the two diabetics with severe autonomic neuropathy indicates that in chronic renal failure irANP secretion may be regulated independently from autonomic influences.

Topics: Adult; Atrial Natriuretic Factor; Diabetic Neuropathies; Dysautonomia, Familial; Humans; Male; Middle Aged; Renal Dialysis; Ultrafiltration; Uremia