Investigation of the vasorelaxant properties of Nitroxyl during altered glycaemic conditions

Abstract

Nitroxyl (HNO) is currently a vasorelaxant of high interest, but as yet its mechanisms of action have not been fully elucidated. It is thought that HNO acts on KV channels to mediate vasorelaxation, and this has been shown in previous studies (Irvine et al, 2003; Favarolo & Kemp-Harper, 2009; Yuill et al, 2011). It has also been shown that high levels of glucose inhibit KV channels (Rainbow et al, 2006) so would inhibit HNO mediated relaxation. This study could provide further evidence of KV involvement of HNO mediated vasodilation. This study uses a temperature controlled organ bath with aortic ring preparations obtained from male Wistar rats, which were killed using approved schedule 1 methods. The section of aorta was connected to an isometric transducer linked to LabChart software. This was used to measure changes in tension in response to the addition of increasing concentrations of sodium nitroprusside (SNP) and Angeli’s salt. These tension changes were quantified and converted to percentage of total relaxation, and presented graphically. The results show that greater relaxation is achieved with Angeli’s salt at high concentrations (>1μM) under normal levels of glucose then under elevated levels of glucose, in both experiments with and without the HNO scavenger L-Cysteine. The lowest level of relaxation achieved was with Angeli’s salt with hydroxocobalamin (HxC) with high levels of glucose present. These results would appear to show that high glucose has the ability to inhibit HNO mediated relaxation. This would further indicate that KV channels are involved in vasorelaxation by HNO, which concurs with data from earlier studies (Irvine et al, 2003; Favarolo & Kemp-Harper, 2009; Yuill et al, 2011; Rainbow et al, 2006).