title: Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy.
abstract: Subclinical hypothyroidism (sHT) is associated with enhanced cardiovascular risk. To test the hypothesis that patients with sHT are characterized by endothelial dysfunction and impaired nitric oxide (NO) availability, in 14 patients [serum cholesterol, 218 +/- 41 mg/dl (5.6 +/- 0.9 mM)] and 28 euthyroid subjects, subdivided into groups A and B [serum cholesterol, 170 +/- 19 mg/dl (4.4 +/- 0.5 mM) and 217 +/- 21 mg/dl (5.6 +/- 0.5 mM), respectively], we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine, an endothelium-dependent vasodilator, at baseline and during infusion of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor. Response to sodium nitroprusside and minimal forearm vascular resistances were also evaluated. In sHT patients, vasodilation to acetylcholine was reduced, compared with group B (+358 +/- 29% vs. +503 +/- 19%, P = 0.0003) and group A (663 +/- 65%, P = 0.02 vs. group B and P = 0.0002 vs. sHT). L-NMMA blunted the vasodilation to acetylcholine in groups A and B (49.1 +/- 6.3% and 42.7 +/- 5.5% maximal forearm blood flow reduction, respectively, P < 0.0001 vs. acetylcholine), whereas it was ineffective in sHT patients (12.8 +/- 2.5%). Response to sodium nitroprusside and minimal vascular resistances were similar. In sHT (n = 9) patients, 6 months of euthyroidism by levothyroxine replacement increased acetylcholine-vasodilation and restored L-NMMA inhibition. Patients with sHT are characterized by endothelial dysfunction resulting from a reduction in NO availability, an alteration partially independent of dyslipidemia and reversed by levothyroxine supplementation.
authors.affiliation: Department of Internal Medicine, University of Pisa, 56100 Pisa, Italy. s.taddei@med.unipi.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Taddei
authors.forename: Nadia
authors.initials: N
authors.lastname: Caraccio
authors.forename: Agostino
authors.initials: A
authors.lastname: Virdis
authors.forename: Angela
authors.initials: A
authors.lastname: Dardano
authors.forename: Daniele
authors.initials: D
authors.lastname: Versari
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghiadoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvetti
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Fabio
authors.initials: F
authors.lastname: Monzani
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy* / Q000503:physiopathology*; D007453:Iodide Peroxidase / Q000276:immunology / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013954:Thyroglobulin / Q000276:immunology / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood; D013967:Thyroiditis, Autoimmune / Q000188:drug therapy / Q000503:physiopathology; D013974:Thyroxine / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D008055:Lipids; D008077:Lipoproteins, LDL; D020030:Nitric Oxide Donors; D013963:Thyroid Hormones; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013954:Thyroglobulin; D007453:Iodide Peroxidase; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D013974:Thyroxine