[PP.12.09] PRESENCE OF RETIGABINE RESPONSE IN HUMAN SUBCUTANEOUS RESISTANCE ARTERIES

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Abstract

Objective:

The aim of this study was to identify a possible response of retigabine, an activator of voltage-gated potassium channels (Kv7-channels), in human subcutaneous resistance arteries. Retigabine has been proved to be a vasodilator in animals, but retigabine response has not earlier been identified in human subcutaneous resistance arteries.

Design and method:

Five healthy men with a normal ambulatory blood pressure had a skin- and subcutaneous adipose tissue biopsy done in their gluteal region after given informed consent. The biopsies were surgically removed and immediately after removal investigated in our laboratory. Small subcutaneous arteries in the biopsies were dissected free from fat and connective tissue under a microscope and mounted in Mulvany-Halpern wire-myographs. After testing for viability endothelial function was tested with acetylcholine (ACh) after precontraction with the prostaglandin PGF2α. After testing for endothelial function cumulative concentration-response curves (CRC) to retigabine were done after precontraction with PGF2α.

Results:

One viable artery from each individual and with similar diameters was selected for analysis. Artery lumen diameter was 360 ± 20 μm (mean ± SEM, n = 5). All of the arteries had intact endothelial function and vasodilatory response to ACh with a pEC50 = 7.95 ± 0.24 (mean ± SEM, n = 5). Furthermore all 5 arteries showed vasodilatory response to retigabine with a pEC50 = 7.89 ± 0.28 (mean ± SEM, n = 5), see attached figure.

Conclusions:

Retigabine exhibits vasodilatory properties in endothelium intact human subcutaneous resistance arteries. The interplay between retigabine and Kv7-channels in human subcutaneous resistance arteries should be explored further in the attempt to find new blood pressure lowering therapies.

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