The Direct Vasomotor Effect of Thyroid Hormones on Rat Skeletal Muscle Resistance Arteries Kyung W. Park, MD*, Hai B. Dai, Mm, Kaie Ojamaa, PhD$, Edward Lowenstein, MD*, Irwin Klein, MDS, and Frank W. Sellke, MD-t Departments of *Anesthesia & Critical Care and tsurgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and $Department of Medicine, North Shore University Hospital, New York University School of Medicine, Mar&asset, New York The present study examines the hypothesis that the hor- mones have direct vasodilatory effects and attempts to determine whether the effects are endothelium- dependent. Rat skeletal muscle resistance arteries of ap- proximately 100 pm were dissected, and vessel diame- ter changes were monitored using a videodetection system. After equilibration at 37”C, each vessel was pre- constricted with the thromboxane analog U46619 1 FM, and the percentage of dilation was measured after ex- posure to increasing concentrations of triiodothyronine (T3) or levothyroxine (T4) (1O@1o to 10F7 M). Dilation in response to T3 was also measured after endothelial denudation and pretreatment with the nitric oxide (NO) synthase inhibitor fl-nitro-L-arginine (L-NNA) 10 FM, the cyclooxygenase inhibitor indomethacin 10 PM, the adenosine triphosphate-sensitive Kt chan- nel blocker glibenclamide 1 PM, or the /3-adrenergic an- tagonist propranolol 1 PM. Both T3 and T4 demon- strated concentration-dependent dilation of the U46619- preconstricted vessels (P < 0.001 each), with T3 having a greater effect than T4 (P < 0.05) (36% ? 9% [mean ? SD] dilation at lop7 M T3 vs 24% 2 6% dilation at lop7 M T4). In comparison, isoproterenol lop7 M produced 56% ? 6% dilation. T3-mediated vasodilation was attenuated but not abolished by endothelial denudation (18% ? 3% dilation at lop7 M T3) (P < O.Ol), L-NNA (15% ? 7% dila- tion at lop7 M T3) (P < O.Ol), indomethacin (20% 5 9% dilation at lop7 M T3) (P < 0.05), and glibenclamide (22% ? 7% dilation at lop7 M T3) (P < O.Ol), but it was not affected by propranolol(37% t 20% dilation at lop7 M T3) (P = 0.99). We conclude that thyroid hormones possess direct vasodilatory effects with both endothelium- independent and endothelium-dependent components. Implications: Thyroid hormones may have modest direct vasodilatory effects. This may partially account for the cardiovascular actions of the hormones in hyperthyroid- ism or when administered pharmacologically in cardiac surgery. (Anesth Analg 1997;85:734-8) T hyroid hormones profoundly alter cardiac func- tion and systemic vascular resistance (1). Al- though the cardiovascular manifestations of thy- roid disease states have been recognized for more than a century, the therapeutic utility of thyroid hormones as cardioactive and/or vasomotor drugs has only re- cently been addressed (2,3). The administration of tri- iodothyronine (T3) to brain-dead organ donors was among the first clinical applications of T3 therapy in which the drug was targeted specifically at improving hemodynamic performance and enhancing organ retrieval (4,5). Supported in part by United States Public Health Service Grant HL-46716 and by a grant from Beth Israel Anesthesia Foundation. Presented in part at the annual meeting of International Anesthe- sia Research Society, San Francisco, CA, March 1997. Accepted for publication June 18, 1997. Address correspondence and reprint requests to Kyung W. Park, MD, Department of Anesthesia & Critical Care, Beth Israel Deacon- ess Medical Center, 330 Brookline Ave., Boston, MA 02215. 734 An&h Analg 1997;85:73&8 In animal models, use of exogenous T3 after cardio- pulmonary bypass improves ventricular performance without oxygen wasting (6,7). Clinical trials of T3 in cardiac surgery have yielded mixed results (S-11), and the routine use of T3 as an inotropic drug in cardiac surgery is not recommended (12,13). How- ever, administration of T3 has been proposed to in- crease cardiac output and to decrease vascular resis- tance in certain clinical settings when conventional inotropic drugs prove insufficient (12). Patients with poor ventricular function may benefit the most from use of T3 through its reduction of the need for conven- tional inotropic drugs (8). Additionally, T3 enhances the recovery of ventricular function after ischemia in exper- imental animals (14). Furthermore, unlike conventional inotropic drugs, which improve cardiac function at the cost of increased oxygen consumption and, thus, de- creased efficiency, T3 may improve cardiac function without additional cost in the myocardial oxygen 01997 by the International Anesthesia Research Society 0003.2999/97/$5.00