Local blood flow regulation in transplanted rat pancreatic islets - Influence of adenosine, angiotensin II, and nitric oxide inhibition

Background. Transplanted islets lack endothelial cells immediately after im plantation and therefore depend on an adequate revascularization for their survival and function. However, the functional properties of the newly form ed islet graft microvessels are largely unknown. This study aimed to invest igate the blood flow regulation of transplanted pancreatic islets. Methods. Pancreatic islets were syngeneically transplanted beneath the rena l capsule of control and streptozotocin-diabetic rats. Blood flow measureme nts were performed 4 weeks later using laser-Doppler flowmetry. Adenosine ( 0.6 mg/kgp1xmin-1), angiotensin II (AT II; 0.17 mu g x kg(-1) x min(-1)) an d the nitric oxide synthase inhibitor N-G-nitro-L-arginine (25 mg/ kg) were given to each animal. Results, An increased basal blood flow and basal vascular conductance in th e islet grafts, but not in the renal cortex, were seen in diabetic rats com pared with control rats. Adenosine increased, and AT II decreased, the vasc ular conductance of the islet grafts in both nondiabetic and diabetic anima ls. A more pronounced circulatory response to AT IP was observed in kidneys of diabetic animals, whereas there was no difference in the islet graft bl ood flow response between nondiabetic and diabetic animals. N-G-Nitro-L-arg inine decreased islet graft blood flow and vascular conductance in both non diabetic and diabetic recipients, but the effect was more pronounced in the nondiabetic animals. Conclusions. Islet graft blood flow was influenced by adenosine, AT II, and nitric oxide inhibition in all animals. However, diabetic animals were les s dependent on nitric oxide to maintain a basal blood flow in the islet gra ft.