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High Glucose Concentrations via Activating Rho‐kinase Leads to Augmented and Sustained Angiotensin II‐induced Arteriolar Constrictions
Author(s) -
Bagi Zsolt,
Kaley Gabor,
Koller Akos
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.732.11
Subject(s) - angiotensin ii , medicine , arteriole , chemistry , endocrinology , angiotensin ii receptor type 1 , rho associated protein kinase , receptor , rhoa , renin–angiotensin system , rho kinase inhibitor , kinase , microcirculation , signal transduction , biochemistry , blood pressure
We tested the hypothesis that functional availability of type 1 angiotensin II (Ang II) receptors (AT1) is enhanced and more sustained in arterioles exposed to high glucose concentration. In isolated, pressurized rat skeletal muscle arterioles (~ 150 μm) Ang II‐induced (10 −8 M) constrictions were measured upon repeated applications in normal glucose (NG, 5.5 mM) or high glucose conditions (HG, 25 mM for 1 hour). Ang II‐induced constrictions to first applications were significantly augmented in HG arterioles (max: 74±6%), compared to NG vessels (max: 56±7%). Upon second applications Ang II‐induced constrictions decreased in NG arterioles (30±6%), but remained substantial in HG vessels (65±9%). In similar protocols constrictions to norepinephrine (10 −7 M) were unaffected by HG exposure. In arterioles, HG caused Rho‐kinase activation, as detected by the increased membrane‐bound RhoA with Western blots. In the presence of Rho‐kinase inhibitor, Y27632 (1 μM) constrictions to first application of Ang II were not significantly different in NG and HG vessels. Moreover, Y27632 reduced constrictions to second applications of Ang II in HG arterioles to the level of NG vessels. These findings indicate that high glucose via activation of Rho‐kinase leads to augmented and maintained Ang II‐induced arteriolar constrictions, which is likely due to a sustained availability of AT1 receptors. (Grants: Hungarian Sci. Res. Funds/OTKA T48376; Am Heart Assoc., NE Aff. T‐0555897, T‐0735540, NIH HL43023).