Nitric oxide mediates abnormal responsiveness of thyroid arteries in methimazole-treated patients.

Abstract:

OBJECTIVE:We studied the intervention of nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) in mediating responses to acetylcholine in thyroid arteries from euthyroid and methimazole-treated (MT) patients. DESIGN AND METHODS:Branches of the superior thyroid artery were obtained from 19 euthyroid patients and 17 MT patients (euthyroid at the time of surgery) undergoing total thyroidectomy or hemithyroidectomy. Artery rings were suspended in organ baths for isometric recording of tension. RESULTS AND CONCLUSIONS:Acetylcholine caused endothelium-dependent relaxation of greater magnitude in arteries from MT patients (pD(2) (-log EC(50)) values were 7.68 +/- 0.19 in euthyroid and 8.17 +/- 0.26 in MT patients, P < 0.05). The relaxation was unaffected by indomethacin and was partially reduced by the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). This reduction was higher in arteries from MT patients (50 +/- 6%) as compared with euthyroid patients (36 +/- 6%) (P < 0.05). Inhibition of K(+) channels using apamin combined with charybdotoxin or high K(+) solution abolished the relaxation resistance to L-NMMA and indomethacin. The maximal contraction response to noradrenaline (as a percentage of the response to 100 mM KCl) was lower in MT than in euthyroid patients (57 +/- 10 and 96 +/- 8 respectively, P < 0.05). The hyporesponsiveness to noradrenaline in arteries from MT patients was corrected by L-NMMA. The results indicate that: (i) thyroid arteries from MT patients show an increased relaxation response to acethylcholine and a decreased contraction response to noradrenaline due to overproduction of NO; (ii) EDHF plays a prominent role in acetylcholine-induced relaxation through activation of Ca(2+)-activated K(+) channels; (iii) the abnormal endothelium-dependent responses in arteries from MT patients are not corrected by medical treatment.

journal_name

Eur J Endocrinol

authors

Ortega J,Vila JM,Mauricio MD,Segarra G,Medina P,Martínez-León JB,Lluch S

doi

10.1530/eje.1.01889

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

551-6

issue

4

eissn

0804-4643

issn

1479-683X

pii

152/4/551

journal_volume

152

pub_type

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