Kv7.1 Channels Contribute to Neonatal Renal Blood Flow Autoregulation Induced by a Step Decrease in Arterial Pressure

Abstract

Kv7 channels, the voltage‐gated potassium channels encoded by KCNQ genes, are expressed in a wide variety of blood vessels, including coronary, mesenteric, cerebral, and renal arteries. In adult rodents, Kv7 channels mediate heterogeneous basal and agonist‐induced vascular reactivity. Although postnatal changes in functional expression of mammalian Kv7 channels have been reported, the physiological significance of these channels in neonatal renal microvessels is unknown. The objective of this study was to determine whether Kv7 channels regulate neonatal renal microcirculation. Polymerase chain reaction indicated that out of the five members of KCNQ genes, only KCNQ1 (Kv7.1) is expressed in smooth muscle cells (SMCs) isolated from preglomerular microvessels of neonatal pigs. Confocal microscopy demonstrated that Kv7.1 is expressed in the plasma membrane of renal vascular SMCs. Kv7.1 channel activators induced whole‐cell currents in neonatal pig renal vascular SMCs, which were inhibited by HMR1556 (HMR), a selective Kv7.1 inhibitor. However, HMR did not cause a significant change in steady‐state diameters of neonatal pig distal interlobular arteries that were pressurized to physiological renal arterial pressure. Also, intrarenal artery infusion of HMR did not alter the mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance in the pigs. An approximately 20 mmHg reduction in the MAP evoked effective autoregulation of the RBF in neonatal pigs, which was inhibited by HMR. Together, these findings suggest that renal vascular SMC Kv7.1 does not control basal renal vascular tone in neonatal pigs, but contribute to RBF autoregulation induced by a step decrease in arterial pressure.Support or Funding InformationAmerican Heart Association (AHA), National Institutes of Health (NIH).