In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 91, No. 12 ( 2006-12-01), p. 5076-5082
Kurzfassung:
Objective: The objective of this study was to assess whether low-grade systemic inflammation might contribute to the pathogenesis of endothelial dysfunction in patients with subclinical hypothyroidism (sHT) and autoimmune thyroiditis. Background: sHT patients are characterized by peripheral endothelial dysfunction and low-grade inflammation. Methods: In 53 sHT and 45 healthy subjects, we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine (Ach) (0.15–15 μg/min·dl) with and without local vascular COX inhibition by intrabrachial indomethacin (50 μg/min·dl) or nitric oxide synthase blockade by N-mono methyl arginine (l-NMMA) (100 μg/min·dl) or the antioxidant vitamin C (8 mg/min·dl). The protocol was repeated 2 h after systemic nonselective COX inhibition (100 mg indomethacin) or selective COX-2 blockade (200 mg celecoxib) oral administrations. Results: sHT patients showed higher C-reactive protein and IL-6 values. In controls, vasodilation to Ach was blunted by l-NMMA and unchanged by vitamin C. In contrast, in sHT, the response to Ach, reduced in comparison with controls, was resistant to l-NMMA and normalized by vitamin C. In these patients, systemic but not local indomethacin normalized vasodilation to Ach and the inhibition of l-NMMA on Ach. Similar results were obtained with celecoxib. When retested after indomethacin administration, vitamin C no longer succeeded in improving vasodilation to Ach in sHT patients. Response to sodium nitroprusside was unchanged by indomethacin or celecoxib. Conclusions: In sHT patients, low-grade chronic inflammation causes endothelial dysfunction and impaired nitric oxide availability by a COX-2-dependent pathway leading to increased production of oxidative stress.
Materialart:
Online-Ressource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/jc.2006-1075
Sprache:
Englisch
Verlag:
The Endocrine Society
Publikationsdatum:
2006
ZDB Id:
2026217-6
