KV7.1 channel blockade inhibits neonatal renal autoregulation triggered by a step decrease in arterial pressure

Am J Physiol Renal Physiol. 2022 Feb 1;322(2):F197-F207. doi: 10.1152/ajprenal.00568.2020. Epub 2022 Jan 10.

Abstract

KV7 channels, the voltage-gated K+ channels encoded by KCNQ genes, mediate heterogeneous vascular responses in rodents. Postnatal changes in the functional expression of KV7 channels have been reported in rodent saphenous arteries, but their physiological function in the neonatal renal vascular bed is unclear. Here, we report that, unlike adult pigs, only KCNQ1 (KV7.1) out of the five members of KCNQ genes was detected in neonatal pig renal microvessels. KCNQ1 is present in fetal pig kidneys as early as day 50 of gestation, and the level of expression remains the same up to postnatal day 21. Activation of renal vascular smooth muscle cell (SMC) KV7.1 stimulated whole cell currents, inhibited by HMR1556 (HMR), a selective KV7.1 blocker. HMR did not change the steady-state diameter of isolated renal microvessels. Similarly, intrarenal artery infusion of HMR did not alter mean arterial pressure, renal blood flow, and renal vascular resistance in the pigs. An ∼20 mmHg reduction in mean arterial pressure evoked effective autoregulation of renal blood flow, which HMR inhibited. We conclude that 1) the expression of KCNQ isoforms in porcine renal microvessels is dependent on kidney maturation, 2) KV7.1 is functionally expressed in neonatal pig renal vascular SMCs, 3) a decrease in arterial pressure up to 20 mmHg induces renal autoregulation in neonatal pigs, and 4) SMC KV7.1 does not control basal renal vascular tone but contributes to neonatal renal autoregulation triggered by a step decrease in arterial pressure.NEW & NOTEWORTHY KV7.1 is present in fetal pig kidneys as early as day 50 of gestation, and the level of expression remains the same up to postnatal day 21. KV7.1 is functionally expressed in neonatal pig renal vascular smooth muscle cells (SMCs). A decrease in arterial pressure up to 20 mmHg induces renal autoregulation in neonatal pigs. Although SMC KV7.1 does not control basal renal vascular resistance, its inhibition blunts neonatal renal autoregulation engendered by a step decrease in arterial pressure.

Keywords: KCNQ; KV7.1; neonates; renal autoregulation; smooth muscle cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Arterial Pressure / drug effects*
  • Chromans / pharmacology*
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Homeostasis
  • KCNQ1 Potassium Channel / antagonists & inhibitors*
  • KCNQ1 Potassium Channel / genetics
  • KCNQ1 Potassium Channel / metabolism
  • Kidney / blood supply*
  • Microvessels / drug effects
  • Microvessels / metabolism
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Potassium Channel Blockers / pharmacology*
  • Renal Circulation / drug effects*
  • Signal Transduction
  • Sulfonamides / pharmacology*
  • Sus scrofa
  • Vasodilation / drug effects*

Substances

  • Chromans
  • HMR 1556
  • KCNQ1 Potassium Channel
  • Potassium Channel Blockers
  • Sulfonamides