Thyroid status and endothelium-dependent vasodilation in skeletal muscle

Abstract

Cardiovascular dysfunction is characteristic of both hypo- and hyperthyroidism. Endothelium-dependent dilation of conductance vessels is impaired in hypothyroidism but augmented in hyperthyroidism. We hypothesized that these alterations in dilation extend into the resistance vasculature of skeletal muscle. To test this hypothesis, rats were made hypothyroid with propylthiouracil (Hypo; n = 13) or hyperthyroid with triiodothyronine (Hyper; n = 9) over 3–4 mo. Compared with euthyroid controls (Eut; n = 14), Hypo rats were characterized by reduced skeletal muscle oxidative capacity and blunted growth; Hyper rats exhibited increased muscle oxidative capacity and left ventricular hypertrophy ( P < 0.05 for all effects). Vasodilation to the endothelium-dependent agent acetylcholine (∼2 × 10⁻⁴ M) in skeletal muscle was determined in situ. Conductance in certain muscles increased from control [e.g., soleus: 0.98 ± 0.15 (Eut), 0.79 ± 0.14 (Hypo), and 1.06 ± 0.24 ml·min⁻¹·100 g⁻¹·mmHg⁻¹ (Hyper); not significant among groups] to acetylcholine [1.91 ± 0.21 (Eut), 2.28 ± 0.26 (Hypo), and 2.15 ± 0.33 ml·min⁻¹·100 g⁻¹·mmHg⁻¹ (Hyper); P < 0.05 vs. control values for all groups] but did not differ among groups. Expression of mRNA for the endothelial isoform of nitric oxide synthase in resistance vessels isolated from various muscles was similarly unchanged with alterations in thyroid status [e.g., soleus 1A arterioles: 33.15 ± 0.58 (Eut), 32.73 ± 0.27 (Hypo), and 32.80 ± 0.54 (Hyper) cycles at threshold; not significant]. These data suggest that endothelium-dependent dilation of resistance vasculature in skeletal muscle is unchanged in both hypo- and hyperthyroidism. These data also emphasize the importance of examining resistance vasculature to improve understanding of effects of chronic disease on integrated cardiovascular function.