Premium
Decreased Functional Vasodilation and Increased Thromboxane Receptor‐mediated Vasoconstriction in Diabetic Rats
Author(s) -
Xiang Lusha,
Abram Sean R,
Hester Robert L
Publication year - 2006
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.20.5.a1150-d
Subject(s) - vasodilation , medicine , endocrinology , vasoconstriction , prostacyclin , thromboxane , thromboxane a2 , arachidonic acid , insulin , streptozotocin , diabetes mellitus , chemistry , receptor , platelet , biochemistry , enzyme
Based on the importance of arachidonic acid (AA) metabolites in functional vasodilation and increased thromboxane/prostacyclin ratio in diabetes, we hypothesize that chronic hyperglycemia (CH) in diabetes increases thromboxane receptor (TP)‐mediated vasoconstriction, attenuating functional vasodilation. Three groups of lean Zucker rats (8 wk old) were used to test the effect of CH: control, streptozotocin (STZ) and STZ + Insulin. Spinotrapezius arcade arterioles were chosen for microcirculatory observation 4 wks later. Arteriolar diameter was measured following muscle stimulation and 10 μM AA application in the absence and presence of 1μM SQ29548 (TP antagonist) and 10 μM indomethacin. Adenosine (10μM) was used to induce a maximal dilation. STZ rats exhibited higher fasting glucose level (385 ± 12 mg/dl), attenuated functional and AA‐induced dilation (90 ± 8%, 75 ± 11%) as compared to control (105 ± 4 mg/dl, 156 ± 10%, 154 ± 13%). Insulin treatment normalized both the glucose level and vasodilatory responses (151 ± 43 mg/dl, 156 ± 19%, 159 ± 4%). Treatment with SQ restored the functional vasodilatory (164 ± 9%) and AA induced (170 ± 14%) responses in STZ rats while had no effect in control or insulin group. In all groups, SQ alone or SQ + Indo did not alter basal diameter, and Indo inhibited the functional and AA‐induced dilation in the presence of SQ. Maximal vasodilation was not different between groups. These results suggest that the impaired dilation in diabetic rats is due to increased TP‐mediated vasoconstriction, which might be secondary to CH. Supported by NIH HL‐51971, HL 63958, AHA SE Postdoctoral Award