Thyroid disease has profound effects on cardiovascular function. Hypo-and hyperthyroidism, for example, are associated with reduced and increased maximal endothelium-dependent vasodilation respectively. We therefore hypothesized that the capacity for vascular nitric oxide (NO) formation is decreased in hypothyroidism and increased in hyperthyroidism. To test this hypothesis, rats were made hypothyroid (HYPO) with propylthiouracil or hyperthyroid (HYPER) with triiodothyronine over 3-4 months. Compared with euthyroid control rats (EUT), HYPO exhibited blunted growth and lower citrate synthase activity in the soleus muscle; HYPER exhibited left ventricular hypertrophy and higher citrate synthase activity in the soleus muscle (P<0·05 for all effects). The capacity for NO formation was determined in aortic extracts by formation of [ . Expression of endothelial and neural isoforms of NOS was modulated by thyroid status in a parallel fashion. Capacity for responding to NO was also determined via measuring cGMP concentration in aortae incubated with sodium nitroprusside. Stimulated cGMP formation was also modulated by thyroid status (EUT, 73·0 20·2 pmol/mg protein; HYPO, 152·4 48·7; HYPER, 10·4 2·6; P<0·05, HYPER vs HYPO). These data indicate that thyroid status alters capacities for both formation of and responding to NO. The former finding may contribute to previous findings concerning vascular function in thyroid disease states.

The presence in the 100,000 g supernatant of rat brain homogenate of an inhibitor of the sialyltransferase has been confirmed. It is also present in chicken and bovine brain and in other rat and bovine organs. The inhibitor has been purified, a preparation with a specific activity 130-fold higher than that of the original 100,000 g supernatant of brain being obtained. It runs as a single peak in polyacrylamide-gel electrophoresis; when run in the presence of SDS, two components appeared. The apparent Mr of the components were 14,800 and 22,400. The inhibitor has been characterized as a heat-stable protein of acidic nature. It has effect on the glycolipid and the glycoprotein sialyltransferase activities but has no effect on the galactosaminyltransferase activity.

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 ϭ 13) or hyperthyroid with triiodothyronine (Hyper; n ϭ 9) over 3-4 mo. Compared with euthyroid controls (Eut; n ϭ 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 Ͻ 0.05 for all effects). Vasodilation to the endothelium-dependent agent acetylcholine (ϳ2 ϫ 10 Ϫ4 M) in skeletal muscle was determined in situ. Conductance in certain muscles increased from control [e.g., soleus: 0.98 Ϯ 0.15 (Eut), 0.79 Ϯ 0.14 (Hypo), and 1.06 Ϯ 0.24 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 ⅐ mmHg Ϫ1 (Hyper); not significant among groups] to acetylcholine [1.91 Ϯ 0.21 (Eut), 2.28 Ϯ 0.26 (Hypo), and 2.15 Ϯ 0.33 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 ⅐ mmHg Ϫ1 (Hyper); P Ͻ 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 Ϯ 0.58 (Eut), 32.73 Ϯ 0.27 (Hypo), and 32.80 Ϯ 0.54 (Hyper) cycles at threshold; not significant]. These data suggest that endotheliumdependent 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.hypothyroidism; hyperthyroidism; acetylcholine; muscle fiber type; nitric oxide synthase BECAUSE HYPOTHYROIDISM AFFECTS nearly 10% of the population (2, 21), it is important to improve the understanding of its underlying pathophysiology. Abnormalities of cardiovascular function are characteristic of the hypothyroid state, and these abnormalities are exacerbated with a stress such as exercise. Our laboratory (11) has found that skeletal muscle blood flow in hypothyroid rats during treadmill running is only 50% of that in their euthyroid counterparts. Consistent with this finding, endothelium-dependent dilation of the conductance-type abdominal aorta has been found to be blunted in hypothyroidism (3, 13). If impaired endothelium-dependent dilation is also characteristic of the resistance vasculature in skeletal muscle, endothelial dysfunction could make an important contribution to blunted muscle blood flow during exercise in hypothyroidism.Cardiovascular function is also abnormal in hyperthyroidism. Interestingly, factors other than cardiovascular dysfunction [e.g., altered patterns of substrate utilization (10)] appear to account for exercise intolerance in this disease state, since s...

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