Patients with hypothyroidism are at a higher risk for coronary vascular disease. 
Patients with diabetes and related vascular complications also have an increased 
incidence of low thyroid function. While thyroid hormones (THs) may be key 
regulators of a healthy vasculature, potential undesirable side effects hinder 
their use in the treatment of vascular disorders. TH analogs such as 
3,5-diiodothyropropionic acid (DITPA) may provide a safer treatment option. 
However, the relative potency of DITPA on vascular growth, cardiac function, and 
metabolism is poorly understood. We hypothesized that the vascular 
growth-promoting effects of DITPA can be obtained with a minimum effect on 
cardiac function. Thyroidectomized Sprague-Dawley rats were given slow-release 
pellets with either thyroxine (T4, 2.7 or 5.2 mg) or DITPA (80 mg) for 6 wk and 
were compared with placebo. Heart mass, body mass, body temperature, serum THs, 
cardiac function (echocardiograms and hemodynamics), and myocardial arteriolar 
density were determined. Hypothyroidism led to reductions in cardiac function, 
heart mass, body temperature, and myocardial arterioles. High-dose T4 prevented 
arteriolar loss and the development of hypothyroidism. Low-dose T4 partially 
prevented the reduction in cardiac function but had minimal effects on 
arteriolar loss. In contrast, DITPA treatment prevented myocardial arteriolar 
loss but not the progression of hypothyroid-induced changes in cardiac function. 
The results suggested that DITPA can promote a healthy vasculature independently 
from its thyroid-related metabolic effects. Drugs in this class may provide new 
therapeutic options for patients with vascular disease.