atrial-natriuretic-factor and Hypoglycemia

We determined the effects of physiological (non-hypotensive) increments of plasma atrial natriuretic factor (ANF) on the vasopressin and hypothalamic-pituitary-adrenal response to insulin induced hypoglycaemia.. Single blind, placebo controlled, randomized study of the effect of vehicle alone or ANF (2.5 pmol/kg/min for 120 minutes) commencing 30 minutes before bolus administration of insulin (0.15 U/kg body weight).. ANF infusion raised venous plasma ANF levels four to five-fold (mean level 32 +/- 0.3 pmol/l at time of insulin injection) without affecting resting blood pressure or heart rate. After insulin, the fall in plasma glucose and rise in plasma adrenaline and noradrenaline were similar in both studies. In contrast, the responses in plasma arginine vasopressin (P < 0.02) and in plasma angiotensin II (P < 0.05) were inhibited by ANF. Plasma corticotrophin releasing factor, ACTH and cortisol responses to hypoglycaemic stress did not differ significantly in the presence and absence of ANF.. We conclude that four to five-fold acute increase in plasma ANF, while attenuating vasopressin and angiotensin II responses to hypoglycaemia, does not inhibit the hypothalamic, pituitary and adrenal responses or inhibit sympathetic nervous activation in normal men.

Topics: Acute Disease; Adrenocorticotropic Hormone; Adult; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Corticotropin-Releasing Hormone; Humans; Hypoglycemia; Hypothalamo-Hypophyseal System; Insulin; Male; Pituitary-Adrenal System; Single-Blind Method

A double-blind placebo-controlled study using the double-dummy technique has been done to examine whether the responses of pituitary and adrenal hormones to insulin-induced hypoglycaemia were impaired by a pharmacological dose of human atrial natriuretic peptide (human ANF-(99-126),hANP). After an overnight fast eight male healthy volunteers (aged 23-40 years) received in random order i.v. bolus injections of insulin 0.125 U.kg-1 + placebo,hANP 100 micrograms + placebo,insulin + hANP, or both placebo preparations. In the insulin-only experiment, human growth hormone, adrenocorticotrophic hormone, cortisol, aldosterone, plasma renin activity, adrenaline, and noradrenaline were all stimulated by hypoglycaemia. In the hANP-only experiment there were no hormonal changes other than decreases in plasma renin activity and aldosterone concentration. In the insulin + hANP experiment the nadir of blood glucose was decreased to 1.3 from the 2.0 mmol.1-1 found in the insulin-only experiment. The exaggerated hypoglycaemia resulted in increased stimulation of human growth hormone, adrenocorticotrophic hormone and adrenaline when compared to the insulin-only experiment. The rise in the cortisol and aldosterone concentrations was only slightly increased, and the stimulation of plasma renin activity was blunted. Unexpectedly, hANP was found to enhance the hypoglycaemic action of insulin, most probably by inhibiting insulin degradation within the liver. There was no evidence of an inhibitory effect of hANP on the stimulation of pituitary or adrenal hormones during insulin-induced hypoglycaemia. The reduction in renin may indicate an inhibitory action of hANP on catecholaminergic effects within the kidney.

Topics: Adrenocorticotropic Hormone; Adult; Aldosterone; Atrial Natriuretic Factor; Blood Glucose; Double-Blind Method; Epinephrine; Growth Hormone; Humans; Hypoglycemia; Insulin; Male; Peptide Fragments; Random Allocation; Renin; Stimulation, Chemical

Insulin-induced hypoglycaemia causes profound haemodynamic changes, commonly ascribed to catecholamine increase. The aim of the present study was to investigate the influence of insulin-induced hypoglycaemia on non-adrenergic factors potentially involved in haemodynamic regulation: angiotensin II and alpha-human atrial natriuretic polypeptide. Fourteen healthy male subjects, aged 25.5 +/- 0.74 years, body mass index 23.81 +/- 0.68 kg/m2, received (after an overnight fast and at least 60 min rest in a supine position) an i.v. bolus injection of human regular insulin (Actrapid HM, Novo, Bagsvaerd, Denmark: 3.84 U/m2). Serial venous blood samples were drawn in the following 150 min, to measure plasma glucose, angiotensin II, alpha-human natriuretic polypeptide, and factors potentially involved in the regulation of the renin-angiotensin-aldosterone system. During the study, we observed a plasma glucose fall, reaching a nadir of 1.95 +/- 0.11 mmol/l between 25 and 30 min, and an increase of angiotensin II (from 7.6 +/- 0.8 to 13.5 +/- 1.1 pg/ml, p = 0.01, quadratic model evaluated by an analysis of the variance for repeated measures), whereas atrial natriuretic polypeptide remained unchanged. As far as the regulation of the renin-angiotensin-aldosterone system is concerned, the increase of angiotensin II is attributable to the increased plasma renin activity, whereas angiotensin converting enzyme was not modified. The increase of plasma renin activity, in turn, is attributable both to the increased catecholamine concentrations and to the decreased potassium levels. Both adrenocorticotropic hormone and angiotensin II are potentially involved in the hypoglycaemia-induced increase of aldosterone concentrations.

Topics: Adrenocorticotropic Hormone; Angiotensin II; Atrial Natriuretic Factor; Blood Glucose; Dopamine; Epinephrine; Humans; Hydrocortisone; Hypoglycemia; Insulin; Kinetics; Male; Norepinephrine; Potassium; Reference Values

The changes in blood glucose, plasma oxytocin, plasma vasopressin, plasma atrial natriuretic peptide, serum osmolality, haematocrit and blood pressure were measured in response to acute insulin-induced hypoglycaemia in six normal male subjects. After the i.v. administration of insulin (0.15 U/kg), plasma concentrations of oxytocin and vasopressin increased rapidly in all subjects and were maximal 15 min after the acute hypoglycaemic reaction (R). Haematocrit increased at the time of the hypoglycaemic reaction, but there was no change in serum osmolality. Systolic blood pressure rose and diastolic blood pressure fell, but mean arterial blood pressure remained unchanged. No changes were demonstrated in plasma concentrations of atrial natriuretic peptide. The release of oxytocin and vasopressin in response to acute hypoglycaemia in man is probably caused by stimulation of the posterior pituitary gland via hypothalamic activation, and not by stimulation of osmoreceptors or baroreceptors.

Topics: Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Hematocrit; Humans; Hypoglycemia; Insulin; Male; Osmolar Concentration; Oxytocin

Topics: Adult; Atrial Natriuretic Factor; Humans; Hypoglycemia; Insulin; Male