Median Preoptic Nucleus Mediates the Cardiovascular Recovery Induced by Hypertonic Saline in Hemorrhagic Shock

Abstract

Changes in plasma osmolarity, through central and peripheral osmoreceptors, activate the median preoptic nucleus (MnPO) that modulates autonomic and neuroendocrine adjustments. The present study sought to determine the participation of MnPO in the cardiovascular recovery induced by hypertonic saline infusion (HSI) in rats submitted to hemorrhagic shock. The recordings of mean arterial pressure (MAP) and renal vascular conductance (RVC) were carried out on male Wistar rats (250–300 g). Hemorrhagic shock was induced by blood withdrawal over 20 min until the MAP values of approximately 60 mmHg were attained. The nanoinjection (100 nL) of GABAA agonist (Muscimol 4 mM; experimental group (EXP)) or isotonic saline (NaCl 150 mM; control (CONT)) into MnPO was performed 2 min prior to intravenous overload of sodium through HSI (3 M NaCl, 1.8 mL/kg, b.wt.). Hemorrhagic shock reduced the MAP in control (62 ± 1.1 mmHg) and EXP (61 ± 0.4 mmHg) equipotently. The inhibition of MnPO impaired MAP (CONT: 104 ± 4.2 versus EXP: 60 ± 6.2 mmHg) and RVC (CONT: 6.4 ± 11.4 versus EXP: -53.5 ± 10.0) recovery 10 min after HSI. The overall results in this study demonstrated, for the first time, that the MnPO plays an essential role in the HSI induced resuscitation during hypovolemic hemorrhagic shock.

Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats

“…Like in the previous study 17 , HSS infusion did not promote plasma volume expansion. Hence, volume replacement seems insufficient to explain cardiovascular hyperosmolarity-induced recovery.…”

“…Moreover, our data showed that the HSS infusion reestablished MAP and HR of sham rats. Several studies have reported HSS infusion-induced hemodynamic improvement after HH 9 , 17 . Highlighting the sympathetic component influence in the hyperosmolarity-responses, the sympathoinhibition generated in the renal territory during HH was maintained after sodium overload.…”

“…The Paxinos & Watson atlas 16 was used to determine the coordinates. For all nanoinjections into the MnPO, a glass micropipette was positioned at 0.6 mm rostral to bregma, 0.0 mm lateral to midline, and 7.2 mm below dura mater 17 . Only animals whose nanoinjections were restricted to the MnPO region were considered for analysis.…”

The median preoptic nucleus: front and centre for the regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis

“…The effect of intravenous hypertonic saline to restore arterial pressure in haemorrhaging animals is also blocked if the MnPO is inhibited by muscimol microinjection (Amaral et al . ). Pharmacological inhibition of AT 1 or NMDA receptors within the MnPO reduces the vasoconstrictor responses to cocaine or ice cold startle in a subgroup (vascular responders) of Sprague–Dawley rats, showing a role for the MnPO in stress‐mediated hemodynamic responses (Schwartz et al .…”

“…Thus, the pressor response to hypertonic saline administered into the carotid artery or ICV can be blocked by injection of losartan, ouabain, b-endorphin or local anaesthetic into the MnPO (Yasuda et al 2000, Budzikowski & Leenen 2001, Stocker & Toney 2005, Caeiro & Vivas 2008, suggestive of an angiotensinergic AT 1 synapse within the MnPO influencing cardiovascular function. The effect of intravenous hypertonic saline to restore arterial pressure in haemorrhaging animals is also blocked if the MnPO is inhibited by muscimol microinjection (Amaral et al 2014). Pharmacological inhibition of AT 1 or NMDA receptors within the MnPO reduces the vasoconstrictor responses to cocaine or ice cold startle in a subgroup (vascular responders) of Sprague-Dawley rats, showing a role for the MnPO in stress-mediated hemodynamic responses (Schwartz et al 2008).…”