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• W2048444015 abstract "Background— Voltage-gated potassium (K + ) channels encoded by KCNQ genes (Kv7 channels) have been identified in various rodent and human blood vessels as key regulators of vascular tone; however, nothing is known about the functional impact of these channels in vascular disease. We ascertained the effect of 3 structurally different activators of Kv7.2 through Kv7.5 channels (BMS-204352, S-1, and retigabine) on blood vessels from normotensive and hypertensive animals. Methods and Results— Precontracted thoracic aorta and mesenteric artery segments from normotensive rats were relaxed by all 3 Kv7 activators, with potencies of BMS-204352=S-1>retigabine. We also tested these agents in the coronary circulation using the Langendorff heart preparation. BMS-204352 and S-1 dose dependently increased coronary perfusion at concentrations between 0.1 and 10 μmol/L, whereas retigabine was effective at 1 to 10 μmol/L. In addition, S-1 increased K + currents in isolated mesenteric artery myocytes. The ability of these agents to relax precontracted vessels, increase coronary flow, or augment K + currents was impaired considerably in tissues isolated from spontaneously hypertensive rats (SHRs). Of the 5 KCNQ genes, only the expression of KCNQ4 was reduced (≈3.7 fold) in SHRs aorta. Kv7.4 protein levels were ≈50% lower in aortas and mesenteric arteries from spontaneously hypertensive rats compared with normotensive vessels. A similar attenuated response to S-1 and decreased Kv7.4 were observed in mesenteric arteries from mice made hypertensive by angiotensin II infusion compared with normotensive controls. Conclusions— In 2 different rat and mouse models of hypertension, the functional impact of Kv7 channels was dramatically downregulated." @default.
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• W2048444015 date "2011-08-02" @default.
• W2048444015 modified "2023-09-24" @default.
• W2048444015 title "Downregulation of Kv7.4 Channel Activity in Primary and Secondary Hypertension" @default.
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• W2048444015 doi "https://doi.org/10.1161/circulationaha.111.032136" @default.
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