Arginine-vasopressin mediates central and peripheral glucose regulation in response to carotid body receptor stimulation with Na-cyanide

Abstract

Arginine-vasopressin mediates central and peripheral glucose regulation in response to carotid body receptor stimulation with Na-cyanide. J Appl Physiol 100: 1902-1909, 2006. First published February 23, 2006 doi:10.1152/japplphysiol.01414.2005.-Hypoxic stimulation of the carotid body receptors (CBR) results in a rapid hyperglycemia with an increase in brain glucose retention. Previous work indicates that neurohypophysectomy inhibits this hyperglycemic response. Here, we show that systemic arginine vasopressin (AVP) induced a transient, but significant, increase in blood glucose levels and increased brain glucose retention, a response similar to that observed after CBR stimulation. Comparable results were obtained after intracerebral infusion of AVP. Systemic AVP-induced changes were maintained in hypophysectomized rats but were not observed after adrenalectomy. Glycemic changes after CBR stimulation were inhibited by pharmacological blockage of AVP V1a receptors with a V1a ]-vasopressin). Importantly, local application of micro-doses of this antagonist to the liver was sufficient to abolish the hyperglycemic response after CBR stimulation. These results suggest that AVP is a mediator of the hyperglycemic reflex and cerebral glucose retention following CBR stimulation. We propose that hepatic activation of AVP V1a receptors is essential for this hyperglycemic response.chemoreceptors; central nervous system respiration RECENT WORK SUGGESTS that the carotid body receptors (CBR), in addition to their classical role sensing O 2 , CO 2 , and pH levels (19,43), also function as receptors of glucose concentration entering the cephalic circulation (1,5,30,41,42). Changes in blood glucose concentration in the carotid sinusbody influence the amount of glucose retained by the brain (6), and the injection of sodium cyanide (NaCN) into the local circulation of the carotid sinus induces a rapid hyperglycemic reflex with a rise in brain glucose retention (1). Unloading of carotid baroreceptors also induces rapid glucose adjustments to regulate plasma osmolality during hemorrhage (28). Experimentally induced low-glucose levels increase catecholamine secretion from carotid body glomus cells in a concentrationdependent manner (41), indicating that this structure is very sensitive to glucose concentration.The efferent pathway for the glycemic reflexes initiated in the carotid sinus region is not fully understood. Previous experiments indicate the participation of the neurohypophysis and adrenal glands, suggesting that the effects of these two glands on CBR hyperglycemic reflexes are humoral (2). A reflex discharge of neurohypophyseal secretion occurs after centripetal stimulation of the vagus nerve (23), and it is known that peripheral receptors connected to the vagus nerve (aortic baro-and chemoreceptors) or associated with the glossopharyngeal nerve (carotid baro-and chemoreceptors) mediate some of their effects through the pituitary (44). It is not known, however, what factors secreted by neurohypophysis are required to elicit...

Intermittent activation of peripheral chemoreceptors in awake rats induces Fos expression in rostral ventrolateral medulla–projecting neurons in the paraventricular nucleus of the hypothalamus

“…The functional significance of OT neurosecretory neuronal activation in relation to cardiovascular responses associated with the chemoreflex remains at present unknown. It is worth mentioning that previous reports documented increased levels of both OT and VP neuropeptides following chemoreflex activation (Share and Levy, 1966; Chen and Du, 1999; Montero et al, 2006). …”

Vasopressin V1a and V1b Receptors: From Molecules to Physiological Systems

“…With regard to the first possible mechanism, the central AVP/V1a receptor signal in the CNS regulates hepatic glucose production. AVP administration into the NTS or cisterna magna induced hyperglycemia (347,464,542). It has also been reported that AVP stimulates GABAergic neurons in vitro (214) and that GABAergic neurons suppress hepatic glucose production (259).…”

Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

“…In addition, direct carotid chemoreceptor stimulation by sodium cyanide was shown to increase hepatic glucose output and increase brain glucose retention within 2 to 8 min, via an adrenal gland- and sinus nerve-dependent manner (35). This same group subsequently demonstrated that the increase in plasma glucose following chemostimulation was mediated via activation of hepatic arginine vasopressin V1a receptors (594) and have since identified both an nNOS-activated mechanism in the hypothalamopituitary axis (125) and a GABA B -mediated mechanism in the nucleus tractus solitarius (518) that may be involved in the regulation of brain and plasma glucose levels following chemoreceptor stimulation. Similarly, intracarotid injections of glucose could significantly attenuate the normal hormonal response to hypoglycaemia (293), although these authors did not consider the reflex to originate from peripheral receptors in the carotid sinus region.…”