Hypertension‐Independent Microvascular Rarefaction in the Obese Zucker Rat Model of the Metabolic Syndrome

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Abstract
Objective: To test the hypothesis that reduced skeletal muscle microvessel density (MVD) in obese Zucker rats (OZR) is independent of chronic elevations in mean arterial pressure (MAP). Methods: Microvessels in cross sections of gastrocnemius muscle from lean Zucker rats (LZR) and OZR were labeled with Griffonia simplicifolia I lectin, visualized with fluorescence microscopy and vessel number within sections was determined using imaging software. Rats were used at different ages to assess correlations between the temporal development of hypertension and microvascular rarefaction. Additionally, rats were chronically treated with captopril or hydralazine as antihypertensive therapies to examine the development of microvascular rarefaction in the absence of elevated blood pressure. Results: MVD in muscle of OZR was reduced by ∼ 17% versus LZR by 10–11 weeks of age, prior to any elevation in MAP. By 15–17 weeks, OZR exhibited a ∼ 23% reduction in MVD and a ∼ 25 mmHg increase in MAP. Treatment with hydralazine prevented elevated MAP in OZR, although this was not associated with an improved MVD. Captopril treatment also prevented elevated MAP in OZR, although a partial recovery of MVD toward normal levels was observed. This observation was associated with an improved insulin resistance. Conclusions: These results suggest that microvessel rarefaction in skeletal muscle of OZR manifesting the metabolic syndrome does not depend on an elevated mean arterial pressure and that other factors associated with the metabolic syndrome, possibly insulin resistance, may underlie the progressive reduction in MVD in these animals.