Attenuation of cryogenic induced brain oedema by arginine vasopressin release inhibitor RU51599

Summary Centrally released arginine vasopressin (AVP) has been implicated in the regulation of the brain water content and is elevated in the cerebrospinal fluid of patients with ischaemic and traumatic brain injuries. The protective effect of RU51599, which is a selective kappa opioid agonist as an AVP release inhibitor, on brain oedema was examined. Male Wistar rats, weighing 300 to 400 g each, were used. The cortical cryogenic injury was produced by application of a previously prepared metal probe cooled with dry ice to the dura of the right patietal region. Animals were separated into three groups. Group 1: sham operated rats without lesion production. Group 2: saline-treated rats with lesion production. Group 3: RU51599-treated rats with lesion production. In Group 3, rats were treated with RU51599 (0.1–3 mg/kg) at 30 minutes before lesion production, 1 hour, 2 hours, and 4 hours after lesion production. After 6 hours, animals were decapitated and brain water contents were measured using the dry-wet weight method. The extent of blood brain barrier (BBB) disruption was determined by assessment of Evans blue uptake based on extraction from tissue using dimethylformamide. The primary injured infarcted area was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Sodium and potassium contents in serum and brain tissue were measured using atomic absorption spectrophotometry. The antagonism of naloxone against protective effects of RU51599 on cryogenic induced brain oedema and on antinociceptive effects in acetic-acid treated animals was examined. Statistical analysis was performed using Dunnett-test and U-test following Kruskal-Wallis test. RU 51599 significantly reduced the brain water contents on the injured side and the contralateral non-injured side (p<0.01) after 4 administration of 1 and 3 mg/kg. RU51599 neither significantly inhibited BBB disruption nor reduced the primary injured infarcted area. RU51559 significantly increased brain sodium and potassium contents in the injured brain and also increased serum sodium levels (p<0.01). Naloxone antagonized the anti-oedema effects and antinociceptive effects of RU51599. These findings indicate that the AVP release inhibitor, RU51599 posssibly mediated by opioid receptors, has a potential protective effect on cryogenic-induced brain oedema and that centrally released AVP plays an important role in the progression of vasogenic brain oedema.     

Sex and oestrous cycle differences in visceromotor responses and vasopressin release in response to colonic distension in male and female rats anaesthetized with halothane{dagger}

Visceromotor responses and vasopressin release before and aftercolonic visceral distension were compared between male (n=5(n=4 for vasopressin)) and female rats and between females duringthe oestrous cycle (proestrus n=6, oestrus n=5, metestrus n=5,diestrus n=6) at a controlled depth of anaesthesia. Pre-stimulationvasopressin and blood pressures demonstrated oestrous cyclevariability. The mean (SEM) colonic balloon pressure triggeringvisceromotor responses was significantly higher in males (64(4) mm Hg) than females (41 (1) mm Hg), P=0.002 and within females,proestrus rats had the lowest thresholds, (29 (1) mm Hg, P<0.01).Post-stimulation, vasopressin concentrations increased significantlyin all groups (males 1.34 (0.39) to 2.24 (0.74) pmol litre^–1;females 1.54 (0.24) to 2.88 (0.58) pmol litre^–1; P=0.002).Within groups statistically significant differences were measuredin proestrus 2.06 (0.56) to 3.42 (1.12) and oestrus 1.16 (0.38)to 2.76 (0.60) pmol litre^–1 (P<0.05). High vasopressinconcentrations coupled with low-pressure stimulation duringproestrus shows sex-hormone dependent integration of the neuroendocrineresponse to noxious visceral stimulation. Br J Anaesth 2000; 85: 907–10