Changes in vasopressin release and autonomic function induced by manipulating forebrain GABAergic signaling under euvolemia and hypovolemia in conscious rats

Abstract

Hypovolemia, as well as hyperosmolality, is a potent stimulus for accelerating arginine vasopressin (AVP) secretion [1]. In contrast to the situation that the cerebral neurons engaged in the hyperosmotic excitation of AVP cells in the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) (AV3V) is a pivotal area for osmotic responses and integration of autonomic functions. The purpose of this study was to investigate whether the gamma-aminobutyric acid (GABA)-ergic activity in the AV3V may be involved in the regulation of arginine vasopressin (AVP) secretion and related phenomena under the conditions with or without hypovolemia. Experiments were performed in conscious rats. We found that AV3V infusion with the GABA A receptor antagonist bicuculline in euvolemic rats caused prompt increases in plasma AVP, osmolality, glucose, arterial pressure and heart rate. The effects of the bicuculline infusion were abolished by prior infusion of a GABA A receptor agonist, muscimol. When repeated twice with a 10-min interval, removal of systemic blood (10 mL/ kg body weight) lowered arterial pressure and enhanced plasma AVP, osmolality, glucose and angiotensin II. Muscimol infusion in the AV3V, but not in the cerebral ventricle, inhibited the responses of plasma AVP and glucose, despite having no effect in a sham hemorrhagic state. The inhibition of the AVP response by the muscimol infusion was also verified in rats given a combined stimulus of bleeding plus an osmotic load. In contrast, AV3V infusion with the GABA B receptor agonist baclofen tended to intensify the hemorrhagic responses of plasma AVP and glucose, despite its potency to prevent the hemorrhagic fall in arterial pressure. These results, taken together with our previous data, suggest that hypovolemic stimuli, like hyperosmotic stimuli, may promote AVP secretion by causing the inhibition of AV3V GABA A -ergic activity responsible for potentiation of glutamatergic activity.Key words: Anteroventral third ventricular region (AV3V), Gamma aminobutyric acid, Antidiuretic hormone, Bleeding, Hypotension information is conveyed from the peripheral organs to the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM) via the carotid sinus or aortic depressor nerve, and then transferred to the SON and PVN through pathways that directly connect these brainstem loci with the hypothalamic nuclei [2-5]. However, there are various observations suggesting that the neurons of the anteroventral third ventricular region (AV3V) responsible for osmotic AVP release may participate in hypovolemic and hypotensive activation of AVP cells. For example, the median preoptic nucleus (MnPO), a major AV3V structure that includes synapses of osmotic circuits [4,6,7], and the subfornical organ (SFO), a neighboring area with osmosensitivity [8], receive afferents from the NTS and VLM (A1 region) [9][10][11][12], and electrical stimulation of the A1 region activates MnPO neurons projecting to the

Development of a hyponatremia screening tool (ABCDF‐S score) for patients with hypertension using thiazide diuretic agents

“…Whether this is a direct or indirect correlation is unclear, and we can only hypothesize about the associated mechanism. This drug has been shown to interact with vasopressinergic neurons due to the effect of the neurotransmitter gamma‐aminobutyric acid . There is one documented case of lorazepam‐induced hyponatremia, caused by induced SIADH .…”

Effects of Drugs and Excipients on Hydration Status

“…In addition, researchers observed synergistic effects between benzodiazepines and diuretics and significant differences between sodium serum levels in patients treated with both thiazides and benzodiazepines, compared to those treated with one or none of these drugs. Regarding the biochemical mechanisms by which benzodiazepines induce hyponatremia, it seems that the gamma-aminobutyric acid (GABA)-ergic activity of benzodiazepines may be involved in vasopressin regulation [181]. Moreover, benzodiazepines are usually prescribed for the treatment of sleep disorders, which are also related to hyponatremia.…”

Quantitative pharmacokinetic–pharmacodynamic modelling of baclofen‐mediated cardiovascular effects using BP and heart rate in rats

“…BP changes can be mediated centrally as well as peripherally. Central GABA B receptor activation in the spinal cord, brainstem and mid brain nuclei modulate changes in BP via multiple mechanisms including sympathetic activation, vagal stimulation and vasopressin release inducing varied responses in BP depending on the site of activation (Amano and Kubo, ; Takenaka et al ., ; Callera et al ., ; Zhang et al ., ; Li and Pan, ; Kobuchi et al ., ; Warner et al ., ; Yamaguchi and Hama, ; Hanafusa et al ., ; Li et al ., ; Wang et al ., ; Rasoulpanah et al ., ). Activation of GABA B receptors in the brainstem increases BP, while activation in the rostral ventrolateral medulla and higher brain nuclei such as paraventricular, ventral tegmental area and ventral medial hypothalamus either decreases or has no effect on BP.…”