Urotensinergic system genes in experimental subarachnoid hemorrhage

Abstract

ObjectiveCerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. DesignAn experimental study was carried out. SettingExperimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). Participants96 Wistar rats: 74 SAH and 22 sham intervention animals. InterventionsDay 1: blood sampling, followed by the percutaneous injection of 100μl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. Main variables of interestWeight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. ResultsSerum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36–1.08]) to day 5 (0.74pg/mL [IQR 0.39–1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06–0.83] day 1; 0.37pg/mL [IQR 0.23–0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06–0.83). ConclusionThe urotensinergic system is upregulated on day 5 in an experimental model of SAH.