Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC244
Effects of high glucose and insulin on vasorelaxation to anandamide
B. Virdee1, D. Zhu1, V. Ho1
1. Division of Biomedical Sciences, St George's University of London, London, United Kingdom.
Endocannabinoids, acting via central and peripheral cannabinoid receptors, are involved in the control of food intake and energy balance. Of note, the metabolic parameters, high glucose and insulin have been shown to modulate the actions and tissue content of anandamide (an endocannabinoid) in pancreatic beta-cells, adipoctyes and serum (1-2). Interestingly, anandamide is also a potent vasorelaxant and has been implicated in blood pressure regulation (3). However, the influence of glucose and insulin on the vascular effects of anandamide remains undetermined. In this study, small mesenteric artery and aorta were isolated from male Wistar rats (200-350g, killed by cervical dislocation) and maintained at 37oC in oxygenated Krebs-Henseleit solution (with 10mM glucose) for isomertric tension recording. Vessels were precontracted with 10µM methoxamine (an α1-adrenoceptor agonist), followed by cumulative additions of anandamide. Data are expressed as mean±s.e.m (n≥4rats) and analysed by Student’s t-tests or 2-way analysis of variance. In the aorta, high glucose (30mM for 1h) significantly reduced relaxation to anandamide (relaxation at 10µM, 10mM glucose = 40±4%; at 30mM glucose = 17±9%; P<0.05). Response to 10µM anandamide was also reduced in the presence of 0.1µM insulin (at 10mM glucose, 16±10%; P<0.05). In contrast, mesenteric relaxation to anandamide was not affected by high glucose (control: pEC50 = 6.97±0.17, Rmax = 106±9%; 30mM glucose: pEC50 = 6.78±0.17, Rmax = 104±6%). Insulin (0.1µM) also had no effect (at 10mM glucose, control: pEC50 = 6.71±0.09, 100±5%; + insulin: pEC50 = 6.70±0.15, Rmax = 109±12%). High glucose also significantly reduced the methoxamine-precontracted tone in aorta (by 39±10%), but not mesenteric artery. To conclude, high glucose and insulin reduce vasorelaxation to anandamide and vasocontraction to methoxamine, depending on the vessel subtype (conduit vs resistance arteries) or vascular region. The compromised anandamide response might contribute to vascular changes seen in hyperglycaemia and/or hyperinsulinaemia.
Where applicable, experiments conform with Society ethical requirements