Role of the endothelial reverse mode sodium-calcium exchanger in the dilation of the rat middle cerebral artery during hypoosmotic hyponatremia.

A decrease in serum sodium ion concentration below 135 mmol L-1 is usually accompanied by a decrease in plasma osmolality (hypoosmotic hyponatremia) and leads to the disorder of intracranial homeostasis mainly due to cellular swelling. Recently, using an in vitro model of hypoosmotic hyponatremia, we have found that a decrease in sodium ion concentration in the perfusate to 121 mmol L-1 relaxes the isolated rat middle cerebral artery (MCA). The aim of the present study was to explore the mechanism responsible for this relaxation. Isolated, pressurized, and perfused MCAs placed in a vessel chamber were subjected to a decrease in sodium ion concentration to 121 mmol L-1. Changes in the diameter of the vessels were monitored with a video camera. The removal of the endothelium and inhibition of nitric oxide-dependent signaling or the reverse mode sodium-calcium exchanger (NCX) were used to study the mechanism of the dilation of the vessel during hyponatremia. The dilation of the MCA (19 ± 5%, p < 0.005) in a low-sodium buffer was absent after removal of the endothelium or administration of the inhibitor of the reverse mode of sodium-calcium exchange and was reversed to constriction after the inhibition of nitric oxide (NO)/cGMP signaling. The dilation of the middle cerebral artery of the rat in a 121 mmol L-1 Na+ buffer depends on NO signaling and reverse mode of sodium-calcium exchange. These results suggest that constriction of large cerebral arteries with impaired NO-dependent signaling may be observed in response to hypoosmotic hyponatremia.

Dysfunction of the endothelium and constriction of the isolated rat's middle cerebral artery in low sodium environment in the presence of vasopressin.

Hyponatraemia, a water-electrolyte disorder diagnosed in patients with subarachnoid haemorrhage (SAH), increases a risk of persistent vasospasm. In majority of cases, hyponatraemia results from inappropriate secretion of vasopressin (AVP). The effect of AVP-associated hyponatraemia on cerebral vasculature is unknown. The present study aimed to elucidate the role of AVP in the response of the middle cerebral artery (MCA) of the rat to hyponatraemia. Isolated, cannulated, and pressurized rat MCAs were perfused/superfused with physiological (Na+  = 144 mmol/L) buffer or low-sodium (Na+  = 121 mmol/L) buffer containing either AVP or angiotensin II (ANG II). ANG II was used to check if the effect of low plasma sodium concentration combined with AVP on the MCA tone is unique to vasopressin. At physiological Na+ concentration, vasopressin (1.4 × 10-11  mol/L) or angiotensin II (10-9  mol/L) resulted in relaxation of the MCA. Substitution of low-sodium for the normal sodium buffer with the same concentration of AVP, resulted in the constriction of the MCA. This effect was absent after removal of the endothelium, administration of vasopressin V1 receptor antagonist or concomitant inhibition of endothelin-1 receptors and synthesis of thromboxane A2. In contrast, no constriction of the MCA in low-sodium buffer was observed when AVP was replaced with ANG II. Our data suggest that presence of vasopressin and low sodium ion concentration results in the change of endothelium phenotype from pro-vasodilatory to pro-vasoconstrictory. This phenomenon may be an overlooked factor contributing to vasospasm in SAH patients with hyponatraemia caused by inappropriate antidiuretic hormone secretion (SIADH).

Morphological changes in the brain during experimental hyponatraemia. Do vasopressin and gender matter?

Hyponatraemia is the most common electrolyte balance disorder occurring in hospitalized patients. The disease results frequently from inappropriate secretion of vasopressin (SIADH). It has been evidenced that the brain consequences of hyponatraemia are more dramatic in young females than in men or postmenopausal women. Since both vasopressin and oestrogen have been reported to inhibit ion fluxes essential for the adaptation of the brain to the lowering of serum sodium concentration, we sought to study the effect of acute and chronic hyponatraemia or hyponatraemia associated with vasopressin on brain morphology in male and female rats. Hyponatraemia was induced with vasopressin (AVP) or with desmopressin (dDAVP) in 12 male and 12 female adult Wistar rats for either 3 hours (acute) or 3.5 days (chronic). The brains of the animals with diagnosed hyponatraemia were fixed in 10% formalin and, following the standard procedure, stained with haematoxylin and eosin. Acute hyponatraemia resulted in white matter oedema with no obvious differences between genders or between groups with AVP- or dDAVP-induced hyponatraemia. Although in chronic hyponatraemia most neurons and astrocytic nuclei appeared to be normal, some neurons were swollen or ischaemic ("dark" neurons) and astrocytes showed a weak reaction. The most spectacular differences between males and females were found in the appearance of blood vessels. Swollen endothelial cells were observed more frequently in female than in male brains and in AVP- than in dDAVP-induced hyponatraemia. The widened Virchow-Robin spaces indicated perivascular oedema and blood-brain barrier damage. The results point to limited vascular adaptation to AVP-associated hyponatraemia in female gender.