Beschreibung:
<jats:p>A hallmark of metabolic disorder is endothelial dysfunction, e.g. lack of dilation to acetylcholine (Ach). We hypothesized that acute elevated glucose alone would reduce endothelial dependent dilation response, yet not effect dilation to exogenous nitric oxide (sodium nitroprusside, SNP). The cremaster muscle of anesthetized (pentobarbital 50 mg/kg) C57BL/6 mice (n=37, 103±18 d, 28±2g) was prepared for intravital microscopy to observe terminal arteriolar diameter. Ach (10‐4 – 10‐9 mM) or SNP (10‐3 – 10‐7) was applied locally via micropipette, before (0 glucose) and after 2 hour continuous exposure to suffusate glucose (15 mM, 270 mg/dl). Responses are reported as change in diameter normalized to maximum (adenosine 10 4 mMol). Maximal dilation with Ach was suppressed with glucose (0.06 ± 0.03) vs. time control (0.35 ± .05). In contrast, maximal dilation with SNP was not different with glucose (0.40 ± .03) vs. time control (0.33 ± 0.04). Mannitol (osmotic control, 15 mM) had no effect on SNP dilation (0.21±.06), yet suppressed Ach dilation (0.02±0.03). Comparing 2 hrs of control suffusate exposure with 2 hours of elevated glucose exposure, the vasoactive response to endothelial dependent dilation is affected by transient diabetic levels of interstitial glucose, while endothelium independent dilation is not. The suppression of Ach response may have osmotic origins. (NIH HL55492, DK68401)</jats:p>