Endothelium‐dependent contractions induced by aging and diet‐induced obesity are attenuated in lipocalin‐2 deficient mice

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AimLevels of Lipocalin‐2, a pro‐inflammatory adipokine, correlates with adiposity, dyslipidemia, hyperglycemia and insulin resistance. The present study evaluates vascular function in mice with deletion of the lipocalin‐2 gene (Lcn2‐KO).MethodsWild type (WT) and Lcn2‐KO mice were fed with standard or high fat diet for 3–17 weeks. Intra‐arterial blood pressure was measured. Isometric tension was measured in carotid artery rings with or without endothelium. Protein expression was measured by Western blotting.ResultsThe obesity‐induced increase in systolic blood pressure was attenuated in Lcn2‐KO mice. In aged or obese WT mice, acetylcholine (ACh)‐elicited endothelium‐dependent contractions were abolished by the COX‐1 selective inhibitor SC560 and the NADH oxidase inhibitor diphenylene iodonium. These contractions were attenuated in Lcn2‐KO mice. ACh‐stimulated superoxide anion production, COX‐1 mRNA and protein expression were decreased in Lcn2‐KO arteries. ACh‐induced production of prostacyclins (PGI2) was lower in Lcn2‐KO preparations. In aged or obese WT mice, PGI2 caused contractions in rings without endothelium but these contractions were reversed to relaxations in Lcn2‐KO arteries.ConclusionsLipocalin‐2 plays an important role in obesity‐induced hypertension and endothelial dysfunction through production of superoxide anions and COX‐1 expression.