Novel role for retinol-binding protein 4 in the regulation of blood pressure

Elevated levels of serum retinol-binding protein 4 (RBP4) contribute to insulin resistance and correlate with increased prevalence of hypertension and myocardial infarction. We sought to determine whether lowering RBP4 would improve blood pressure (BP) and protect against obesity- or angiotensin (Ang)-II-induced hypertension. Systolic and diastolic BP were lower in the RBP4-knockout (RBP4-KO) mice and higher in the RBP4- overexpressing (RBP4-Tg) mice compared with BP in the wild-type (WT) littermates. Carbachol-induced vasodilatation was increased in arteries from the RBP4-KO compared with the WT mice and was impaired in the RBP4-Tg mice. Aortic eNOS^Ser1177 phosphorylation was enhanced ∼50%in theRBP4-KOmice, with no change in total eNOS protein. Feeding a high-fat diet increased BP in the RBP4- KOmice only to the level in theWTmice fed chow and had no effect on aortic eNOS^Ser1177 phosphorylation. Ang-II infusion resulted in 22 mmHg lower systolic BP in the RBP4-KO than in the WT mice, although the relative BP increase over saline infusion was ∼30% in both. Ang-II treatment decreased aortic eNOS^Ser1177 phosphorylation in the WT and RBP4-KO mice, but phosphorylation remained higher in the RBP4-KO mice. Cardiac hypertrophy with Ang-II treatment was diminished by 56% in the RBP4- KO mice. Thus, elevated serum RBP4 raises BP and lack of RBP4 reduces it, with commensurate changes in aortic eNOS^Ser1177 phosphorylation. Lowering RBP4 may reduce BP through enhanced eNOS-mediated vasodilatation and may be a novel therapeutic approach for hypertension.- Kraus,B. J., Sartoretto, J.L.,Polak,P.,Hosooka,T., Shiroto,T., Eskurza, I., Lee, S.-A., Jiang, H.,Michel, T., Kahn, B. B. Novel role for retinol-binding protein 4 in the regulation of blood pressure.