Increasing evidence suggests that atrial natriuretic peptide (ANP), a 28-amino acid peptide with biologically active 4-28 and 5-28 congeners modulates salt-water homeostasis at both peripheral and central levels. In rats, immunoreactive (ir) ANP is found in hypothalamic (HT) neurons of preoptic and paraventricular regions rich in aminergic innervation. Employing a well-characterized perifusion model of rat HT explants, the acute effects of norepinephrine (NE) on HT release of irANP were examined. Pulsatile administration (20 min) of NE(10-7 to 10-5 M) induced a dose-related release of irANP. The stimulatory effect of 10-5 M NE (2.66 ± 0.54 pg/ml/HT, means ± SE, n = 12) was abolished in the presence of 10-7 M propranolol, a β-antagonist, but was 50% higher when administered with 10-5 M phentolamine, an α-antagonist. Administration of equivalent doses of propranolol or phentolamine alone, consistently suppressed (40% below basal secretion rate, BSR) or stimulated (50% above BSR) irANP release, respectively. In addition, infusion of isoprenaline (10-5 M), a β-agonist, enhanced BSR by 45%, whilst phenylephrine (10-5 M), an α-agonist, suppressed it by 25%. We conclude that in rat hypothalami (1) occupancy of the β-adrenoceptor by its agonist stimulates irANP release, (2) α- and β-adrenoceptors modulate irANP secretion in an opposing manner, and (3) the basal release of irANP is a product of the activation of α- and β-adrenoceptors by their endogenous ligands.
- atrial natriuretic peptide