Essential role of hypothalamic muscarinic and alpha-adrenergic receptors in atrial natriuretic peptide release induced by blood volume expansion.

Abstract

Expansion of the blood volume induces natriuresis, which tends to return the blood volume to normal. This response is mediated at least in part by the release of atrial natriuretic peptide (ANP) into the circulation. Previous experinents have shown the participation of the anterior ventral third ventricular (AV3V) region of the hypothalamus in the ANP release that follows volume expansion. When injected into the AV3V region, the cholinergic drug carbachol induces natriuresis and the release of ANP. In the present experiments, microinjection of norepinephrine into the AV3V region induced natriuresis and an increase in plasma ANP. To determine whether cholinergic and a-adrenergic pathways are crucial to the volume expansion-induced release of ANP, certain receptor-blocking drugs were injected into the AV3V region ofconscious rats. Thirty minutes later blood volume was expanded by intravenous injection of 2.0 ml/100 g of body weight of hypertonic saline (0.3 M NaCI). Microinjection of isotonic saline (2 gd) into AV3V region of control animals 30 min prior to volume expansion had no effect on the 3-fold increase in plasma ANP concentrations measured 5 min after volume expansion. In contrast, although the receptor-blocking drugs did not alter the initial concentrations of plasma ANP 30 min later, just prior to volume expansion, blockade of muscarinic cholinergic receptors by intraventricular injection of 5 nmol (2 id) of atropine sulfate or methylatropine markedly reduced the response to volume expansion but did not obliterate it. Microinjection of the a receptor blocker phentolamine (5 nmol) into the AV3V 30 min prior to volume expansion also markedly suppressed the ANP response. Intraperitoneal (i.p.) injection of methylatropine (0.01 mmol/100 g of body weight), which does not cross the blood-brain barrier, also did not affect the basal levels of ANP 30 min after i.p. injection. But, in striking contrast with the blockade of the response to volume expansion induced by intraventricular injection of methylatropine, the response to volume expansion was markedly enhanced by i.p. injection of methylatropine. The results therefore indicate that hypothalamic muscarinic and a-adrenergic synapses are essential to release of ANP in response to volume expansion. These results are consistent with a hypothetical pathway for physiological control of ANP release which involves distension of baroreceptors within the right atria, carotid and aortic sinuses, and kidney which alters afferent input to brain stem noradrenergic neurons with axons projecting to the AV3V region. There they activate cholinergic interneurons by an a1-adrenergic synapse. The cholinergic neurons in turn stimulate ANP neurons in this brain region via muscarinic receptors. The stimulation of these neurons activates efferent pathways which induce the release of ANP.The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to...

Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

“…Consistent with these findings, nanoinjection of norepinephine into the MnPO, the major source of AV3V efferents, increased renal sodium excretion (60) and ANP release, whereas acute pharmacological blockade of α1-adrenoceptors in the AV3V reduced the ANP release induced by blood volume expansion (40). Therefore, we hypothesized that noradrenergic neurotransmission from the A1 noradrenergic group to the MnPO may be involved in the cardiovascular responses to hypernatremia.…”

“…The preoptic-periventricular tissue surrounding the anteroventral third ventricle (AV3V) is a forebrain region with a critical role in the maintenance of fluid and electrolyte balance and cardiovascular function (7,(38)(39)(40)(41)(42)(43)(44). The AV3V received its name because of its location just anteroventral (AV) to the third ventricle (3V).…”

The neuroendocrine control of atrial natriuretic peptide release

“…Because a common denominator of the lesion was the elimination blocker, phentolamine (5 nmol in 2 l saline). 45 We have illustrated the putative pathway of actiof the brain ANP neuronal system, these results suggest that the brain ANP plays a role in the mediation of the vation of ANP release and natriuresis via BVE (Figure 1). It involves distension of baroreceptors in the release of ANP that occurs after volume expansion.…”

Neuroendocrine control of body fluid homeostasis

“…Atropine also had no effect on basal levels of plasma ANP, but in striking contrast to the blockade of the response to volume expansion induced by intraventricular injection of methyl atropine, the response to volume expansion was markedly enhanced by ip injection of methyl atropine. The results therefore indicate that hypothalamic muscarinic and a-adrenergic synapses are essential for ANP release in response to volume expansion (43). The ability of methyl atropine, a blocker of peripheral cholinergic receptors, to augment the response suggests an inhibitory role of vagal cholinergic efferents in ANP release.…”

“…These blockers had no effect on resting levels of the hormone just prior to BVE; however, a highly significant blockade of the responses was induced by the prior injection of the muscarinic cholinergic receptor blockers, atropine sulfate (5 nmol in 2 µl 0.9% NaCl) or methyl atropine at a similar dose. Microinjection of the areceptor blocker, phentolamine (5 nmol in 2 µl saline) also markedly suppressed the ANP response (43).…”