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 (2log 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 þ channels using apamin combined with charybdotoxin or high K þ 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 2þ -activated K þ channels; (iii) the abnormal endothelium-dependent responses in arteries from MT patients are not corrected by medical treatment.European Journal of Endocrinology 152 551-556

Enhancement of endothelium‐dependent flow‐mediated vasodilation in hyperthyroidism

“…This study demonstrated that endothelium‐dependent FMD was greater in hyperthyroid patients than in controls. In agreement with human studies, forearm blood flow and relaxation of thyroid arteries in response to acetylcholine are increased in hyperthyroid patients 23,24 . However, findings obtained in this study are in conflict with a human study showing that the FMD values decreased in subclinical hypothyroidism or hyperthyroidism 25 .…”

“…The vascular segments of hyperthyroid rodents relaxation in response to acethylcholine were decreased or unchanged in some studies, 18–21 whereas other studies reported that these animals had increased relaxation responding to acetylcholine 4–9 . Reports regarding vascular response in patients with hyperthyroidism are limited 23,24 . This is the first study using FMD as a noninvasive indicator of vascular endothelial function to evaluate hyperthyroid patients during the hyperthyroid state and their euthyroid state following treatment with antithyroid agents.…”

Evaluation of endothelial function in exogenous subclinical hyperthyroidism and the effect of treatment

“…[2526] Partial restoration of FMD when treating hyperthyroid patients may be due to increase of endothelium-derived hyperpolarizing factor in hyperthyroid patients, which cannot be corrected by treatment. [27] In our study, we illustrate that FMD changes are not related to hypothyroidism background because after reduce dose of levothyroxine, FMD became better than past.…”

Contractile responses of human thyroid arteries to vasopressin

“…Such data might be of pathophysiological significance in those states characterised by increased plasma vasopressin levels, such as haemorrhagic and septic shock (Landry et al, 1997;Tsuneyoshi et al, 2003) and in some patients with congestive heart failure (Rouleau et al, 1994;Goldsmith and Gheorghiade, 2005). Studies from our laboratory have shown that in human thyroid arteries from multiorgan donors the endothelium modulates responses to acetylcholine and noradrenaline through the release of nitric oxide (NO), an endothelium-derived relaxing factor (Torondel et al, 2004;Ortega et al, 2005). Moreover, NO production is decreased in hyperthyroid patients when compared with control subjects (Hermenegildo et al, 2002).…”