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

Abstract

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).

Compromised regulation of the rat brain parenchymal arterioles in vasopressin‐associated acute hyponatremia

“…Our previous studies have shown that the constriction of the MCA in AVP‐associated hyponatremia depends on endothelin‐1 and thromboxane A 2. 40 The mechanism of the constriction of parenchymal arterioles during AVP‐associated hyponatremia is unknown at present. Taking into consideration substantial functional and structural differences between parenchymal arterioles and pial arteries 14,15,19,20 it is unlikely that the mechanism of constriction of both types of vessels during AVP‐associated hyponatremia is identical.…”

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

“…Recently, we have found that lowering the extracellular concentration of Na + to the level diagnosed in symptomatic patients with hyponatremia (121 mmol L − 1 ), elicits dilation of the rat middle cerebral artery [22]. In the present study, we sought to identify the possible mechanism responsible for this dilation.…”

“…Isolation and mounting of the MCA Middle cerebral arteries (n = 76) were isolated and mounted in the organ chamber according to the procedure as described [22]. Brie y, MCA was dissected and cleaned of connective tissue.…”

Vasopressin: a possible link between hypoxia and hypertension

“…In the cerebral circulation, vasopressin can cause either increase of the blood flow through an action mediated by V2Rs [85] or restriction of the flow, presumably through stimulation of V1Rs. Interestingly, it appears that the vasoconstrictory action of vasopressin in the cerebral circulation may predominate in hyponatremia, which is an unavoidable attribute of SIADH [168,169]. The traumatic brain injury which is associated with hypoxia causes significant increase of V1aR in the frontoparietal cortex [104].…”