ROLE OF IN VIVOVASCULAR REDOX IN RESISTANCE ARTERIES

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2014-10, Vol.65 (1), p.130-139
• Main Authors: Hilgers, Rob H.P., Das, Kumuda C.
• Format: Article
• Language: English
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.114.04473

Vascular thiol redox state has been shown to modulate vasodilator functions in large conductance Ca 2+ -activated K + channels and other related channels. However, the role of vascular redox in small resistance arteries is unknown. To determine how in vivo modulation of thiol redox state impacts small resistance arteries relaxation we generated a transgenic mouse strain that overexpress thioredoxin (Trx), a small redox protein (Trx-Tg) and another strain that is Trx-deficient (dnTrx-Tg). The redox state of the mesenteric arteries (MAs) in Trx-Tg mice is found to be predominantly in reduced state; in contrast, MAs from dnTrx-Tg mice remain in oxidized state. Thus, we created an in vivo redox system of mice and isolated the 2 nd -order branches of the main superior MAs from wildtype (wt), Trx-Tg or dnTrx-Tg mice to assess endothelium-dependent relaxing responsesin a wire-myograph. In MAs isolated from Trx-Tg mice we observed an enhanced IK1 channel contribution resulting in a larger endothelium-dependent hyperpolarizing (EDH) relaxation in response to indirect (ACh) and direct (NS309) opening of endothelial K Ca channels. MAs derived from dnTrx-Tg mice showed both blunted NO-mediated and EDH-mediated relaxation compared to Trx-Tg mice. In a control study, diamide decreased EDH relaxations in wt mice MAs, whereas DTT improved EDH relaxations, and was able to restore the diamide-induced impairment in EDH response. Further, the basal or angiotensin II-mediated systolic blood pressure remained significantly lower in Trx-Tg mice compared to wt or dnTrx-Tg mice; thus, directly establishing redox-mediated EDHF in blood pressure control.