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

Abstract

Background: Transplanted islets lack endothelial cells immediately after implantation and therefore depend on an adequate revascularization for their survival and function. However, the functional properties of the newly formed islet graft microvessels are largely unknown. This study aimed to investigate the blood flow regulation of transplanted pancreatic islets.

Methods: Pancreatic islets were syngeneically transplanted beneath the renal capsule of control and streptozotocin-diabetic rats. Blood flow measurements were performed 4 weeks later using laser-Doppler flowmetry. Adenosine (0.6 mg x kg(-1) x min(-1), angiotensin II (AT II; 0.17 microg x kg(-1) x min(-1)) and the nitric oxide synthase inhibitor NG-nitro-L-arginine (25 mg/ kg) were given to each animal.

Results: An increased basal blood flow and basal vascular conductance in the islet grafts, but not in the renal cortex, were seen in diabetic rats compared with control rats. Adenosine increased, and AT II decreased, the vascular conductance of the islet grafts in both nondiabetic and diabetic animals. A more pronounced circulatory response to AT II was observed in kidneys of diabetic animals, whereas there was no difference in the islet graft blood flow response between nondiabetic and diabetic animals. NG-Nitro-L-arginine decreased islet graft blood flow and vascular conductance in both nondiabetic and diabetic recipients, but the effect was more pronounced in the non-diabetic animals.

Conclusions: Islet graft blood flow was influenced by adenosine, AT II, and nitric oxide inhibition in all animals. However, diabetic animals were less dependent on nitric oxide to maintain a basal blood flow in the islet graft.