Possible Role of Endothelin Acting within the Hypothalamus to Induce the Release of Atrial Natriuretic Peptide and Natriuresis

Abstract

Since endothelin has been localized in neurons in areas involved in water and electrolyte metabolism, areas which also contain atrial natriuretic peptide (ANP) neurons, we determined whether endothelin would release ANP and induce natriuresis. Endothelin-3 (ET-3) in doses ranging from 38 to 760 pmol was microinjected into the third ventricle (3V) of conscious, water-loaded male rats, and the effect on natriuresis and plasma ANP was determined. ET-3 evoked a dose-related natriuresis beginning within 20 min of injection. Even the lowest dose tested (38 pmol) was effective. At a dose of 95 pmol, it produced a rapid increase of plasma ANP within 5 min peaking at 20 min. A slight kaliuresis and antidiuresis was observed at the 2 highest doses of 380 and 760 pmol. The urinary changes following 3V injection of ET-3 were similar to those evoked by ANP, except for the antidiuresis with increased sodium concentration which followed injection of the 2 higher doses. These results suggest that these 2 higher doses also released vasopressin. Alternatively, activation of the sympathetic nervous system by these higher doses may have decreased glomerular filtration rate and been in part responsible for the antidiuresis. The results with 3V injection of ET-3 contrasted sharply with those obtained following intravenous injection of the 95-pmol dose injected intra-ventricularly. This intravenous dose of ANP induced a transient decrease in sodium and potassium excretion and urine volume, maximal at 20 min, and had no effect on plasma ANP concentrations at 5 or 20 min after injection. Previous experiments have shown that the hypothalamic ANP neuronal system plays an essential role in the volume expansion-induced release of ANP and the subsequent natriuresis. We speculate that endothelin released in the brain following volume expansion may activate the ANP neuronal system which is then followed by an increased release of ANP from the atria and possibly from the brain. Further experiments will be necessary to validate this hypothesis.

Brain Natriuretic Peptide and Cerebral Vasospasm in Subarachnoid Hemorrhage

“…28,29 In addition, endothelin has been identified in hypothalamic neurons involved in water and electrolyte metabolism and has been proved to induce natriuresis. 30 It is therefore plausible that the release of endothelin induced by the initial vascular damage may account for both BNP secretion and vasospasm.…”

Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart

“…There is considerable evidence that the central nervous system is critically involved in release of the cardiac hormone atrial natriuretic peptide (ANP) in response to volume expansion (1)(2)(3)(4). For example, lesions in the median eminence or neural lobe of the pituitary gland which interrupt neuronal projections to the neurohypophysis, thereby blocking the release of neurohypophyseal hormones, block volume expansioninduced ANP release (5).…”

Atrial natriuretic peptide and feeding activity patterns in rats

“…Despite the blood-brain barrier, these systems communicate through the circumventricular organs, the organum vasculosum lamina terminalis and the organum subfornicalis (7)(8)(9). They are connected by neuronal synapses (9)(10)(11)(12)(13)(14), or by discharge of peptides such as vasopressin (15), endothelin (11) and oxytocin (16) from the hypothalamus. Therefore, ANP may participate in the control of different functions such as the reduction of the activity of the renin-angiotensin-aldosterone system and inhibition of salt and water intake in the rat (17,18).…”

“…ANP and the HPA-A Two lines of research have been exhaustively followed by our group since the early eighties. First, the investigation involved the brain ANPergic neuron system and its role as antagonist of the renin-angiotensin system, its influence on ANP release including ANP release induced by volume expansion (9)(10)(11)(12)(13)(14)(17)(18), and other hormonal effects of the brain ANP system on LH, prolactin, GH, TSH, and ACTH secretion (20,24). In parallel, we investigated the circadian rhythmicity of the hypothalamic-pituitary-adrenal axis (HPA-A) in rats with continuous or restricted access to food (27).…”