The effect of human atrial natriuretic peptide on renal and cardiovascular responses to insulin-induced hypoglycemia in healthy man

Summary

In healthy men insulin-induced hypoglycemia offers the opportunity to examine under nearly physiologic conditions the potential effects of human atrial natriuretic peptide (human ANF- (99–126), hANP) on catecholamine- or vasopressin-related events. Thus, evidence is presented that 100 μg hANP given as an i.v. bolus injection does not inhibit the counter-regulatory increase in epinephrine and norepinephrine concentrations in plasma in response to decreased blood glucose levels. However, hANP is found to inhibit, by direct or indirect mechanisms, the epinephrine-mediated increase in heart rate and systolic blood pressure and to antagonize the action predominantly of norepinephrine on diastolic blood pressure. Whereas the sodium-retaining effect of insulin-induced hypoglycemia is completely reversed by hANP, its anti-diuretic effect is only partially suppressed. It appears likely that under physiologic conditions the antagonizing action of hANP on the renal response to vasopressin is more prominent than its potential capacity to inhibit vasopressin secretion. Moreover, hANP is found to increase the effectiveness of exogenous insulin. This is probably predominantly due to its inhibiting effect on the hepatic insulin break-down.

In endocrinological research, insulin-induced hypoglycemia is a well-defined and thoroughly studied experimental model for investigating the effects of metabolic stress on hormonal systems. The concomitant stimulation by insulin-induced hypoglycemia of the release of vasopressin, epinephrine and norepinephrine is part of its most prominent hormonal characteristics (1,2). Therefore, insulin-induced hypoglycemia offers the unique opportunity to examine in healthy man under nearly physiological conditions whether human atrial natriuretic peptide (human ANF-(99–126), hANP) is capable of influencing the release or the effects of raised concentrations of these hormones on renal and cardiovascular indexes.