Introduction: Increased intracranial pressure (ICP) results in compression of brain structures and decreased cerebral blood flow [1]. The diminished cerebral perfusion is compensated for by Cushing reflex, which maintains cerebral perfusion pressure (CPP) via elevation of arterial blood pressure [2]. Arginine vasopressin (AVP) is a potent vasopressor neurohormone with vasoconstrictive and central effects mediated by vasopressin type 1a receptor (V1a) [3]. AVP is also involved in the pathogenesis of brain oedema resulting in high ICP [4]. Clinical reports point to beneficial effects of blockade of vasopressin receptors in treatment of brain oedema [5], however, there is a limited evidence on the role of vasopressin in the Cushing response, which maintains CPP. Aim: In the present study we investigate the role of brain and peripheral vasopressin V1a receptors in Cushing reflex. Methods: We implanted adult male Sprague-Dawley rats with arterial and venous catheters for recording of blood pressure and administration of drugs, and with two steel cannulae into the lateral cerebral ventricles (LCV) for intrabrain infusions and measurement of ICP. We recorded mean arterial blood pressure (MABP), heart rate, ICP and CPP. After measurements at rest, saline (10 μL/30sec) or V1a receptor antagonist (d(CH2)51,Tyr(Me)2,Arg8)-Vasopressin; 500 ng/10μl/30 sec) was infused into LCV and after 5 min ICP was gradually increased by LCV infusion of 0.9% NaCl at the rate of 60 µl/min till obtaining ICP of 100 mm Hg. In another group of rats we intravenously administered saline (100 μl/30 sec) or V1aR antagonist (5 μg/100 μl/30 sec). All procedures and measurements were performed under anaesthesia (1.5 g/kg b.w., i.p.). We also collected blood samples before elevation of ICP and at the peak increase in ICP. Using enzyme-linked immunosorbent assays we measured serum copeptin, fragment of proAVP stoichiometrically released with AVP, and serum norepinephrine. Results: Increase of ICP resulted in a significant increase of serum copeptin and serum norepinephrine (p<0.05). Neither intravenous nor intracerebroventricular administration of V1a receptor antagonist changed MABP before the elevation of ICP. Acute increase in ICP led to increase in MABP and resulted in a similar decrease in CPP in all groups. Neither peripheral nor central bockade of V1a receptors affected CPP and hemodynamic parameters during ICP increase. Conclusions: Our results show that Cushing response to acute increase in ICP effectively limits decrease in CPP, regardless of blockade of central or peripheral V1a receptors. Lack of the effect of vasopressin receptor antagonists on Cushing reflex may prove beneficial for mainaining cerebral perfusion in patients with increased ICP.