Vascular Protective Action of GLP‐1 in Vivo

Human studies suggest that GLP‐1 protects cardiovascular function. No data are available in the literature to explain this beneficial action of GLP‐1. We studied the impact of GLP‐1 on leukocyte‐endothelium interaction (LEI), an important determinant of vascular pathology. LEI were measured by intravital microscopy in mesenteric post‐capillary venules of live C57BL/6 mice. Endothelial dysfunction was induced by a 14‐day administration of 50 mg/kg/day of the eNOS inhibitor L‐NAME in the drinking water. GLP‐1 was administered subcutaneously at the dose of 280 ng/kg/hr via osmotic minipumps, for 3 consecutive days before study. L‐NAME increased the number of rolling and adherent leukocytes (63±4.7 vs 39±2.5 cells/min and 7.3±2.1 vs. 2.5±0.4 cells/100 μm, respectively; p<0.01 vs. control). GLP‐1 significantly attenuated L‐NAME‐induced leukocyte rolling to 40±4.4 cells/min and adherence to 2.4±0.3 cells/100 μm (NS versus control). Western blot analysis revealed decreased eNOS phosphorylation and increased ICAM‐1 expression in the mesenteric vasculature of mice given L‐NAME, which was attenuated by GLP‐1 treatment. No significant changes were observed in body weights, white blood cell counts, and plasma glucose in all groups of mice. Thus, GLP‐1 protects vascular function in part via inhibition of LEI, and independently of metabolic actions. Supported by a W.W. Smith Trust research grant.