Beta-hydroxybutyrate-induced vasodilation is mediated by Kv7 potassium channels

Despite the conflicting reports on ketogenic interventions at lowering blood pressure and ameliorating hypertension, we have previously demonstrated that the most abundant ketone body, β-hydroxybutyrate (βOHB) is a novel vasodilator. While the G-protein couple receptors, Gpr109 and Gpr41, are the canonical receptors for βOHB, they do not mediate βOHB-induced vasodilation. On the other hand, it has been observed in central nervous system that βOHB can activate potassium channels of the K V 7 family such as KCNQ1, KCNQ2, and KCNQ3. In addition, the presence of K V 7 channels has been observed in the endothelial cells. Therefore, we hypothesized that βOHB-induced vasodilation was mediated through K V 7 potassium channels. To examine this, we analyzed βOHB-induced vasodilation in mesenteric resistance arteries (MRA) of 12-15 week old male Wistar rats (n=4-14) in the presence of three different K V 7 inhibitors, Linopiridine dihydrochloride (10 -5 M), XE991 dihydrochloride (10 -6 M), or 4-Amino-3-hydroxybutyric Acid (10 -4 M), using wire myography. We observed that each inhibitor stifled the relaxing effects of βOHB Linopiridine dihydrochloride [AUC control 240 ±31.7, vs. Linopiridine dihydrochloride 74.61 ±26.7, p<0.05], XE991 dihydrochloride [AUC control 240 ±31.7, vs. XE991 dihydrochloride 101.6 ±35.3, p<0.05], and 4-Amino-3-hydroxybutyric Acid [AUC control 240 ±31.7, vs. 4-Amino-3-hydroxybutyric Acid 71.3 ±31.3, p<0.05]. Overall, these data suggest that βOHB propagates vasodilation through non-canonical K V 7 channels. Funding: R00GM118885, R01HL149762, R00HL151889, and NHLBI (R00HL151889) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.