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Published on: October 26, 2020
KV7.1 channel blockade inhibits neonatal renal autoregulation triggered by a step decrease in arterial pressure
Dieniffer Peixoto-Neves1, Praghalathan Kanthakumar1, Jeremiah M Afolabi1
1Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee.
Neonatal pig renal microvessels express KV7.1 channels, which do not control basal tone but are crucial for renal autoregulation following a drop in blood pressure.
Area of Science:
- Physiology
- Cardiovascular Research
- Renal Physiology
Background:
- KV7 channels (encoded by KCNQ genes) influence vascular responses, but their role in the neonatal kidney is unknown.
- Previous studies show postnatal changes in KV7 channel expression in rodent arteries.
Purpose of the Study:
- To investigate the expression and function of KCNQ isoforms in neonatal pig renal microvessels.
- To determine the role of KV7.1 in renal vascular tone and autoregulation in neonatal pigs.
Main Methods:
- Detected KCNQ gene expression in neonatal pig renal microvessels.
- Activated KV7.1 channels in smooth muscle cells and assessed effects using a selective blocker (HMR1556).
- Measured effects of HMR1556 on isolated microvessels, arterial pressure, renal blood flow, and renal vascular resistance during autoregulation challenges.
Main Results:
- Only KCNQ1 (KV7.1) was detected in neonatal pig renal microvessels, present from gestation day 50 to postnatal day 21.
- KV7.1 activation produced currents in smooth muscle cells, inhibited by HMR1556.
- HMR1556 did not affect basal renal vascular tone but inhibited renal autoregulation following a 20 mmHg reduction in mean arterial pressure.
Conclusions:
- KCNQ isoform expression in porcine renal microvessels is maturation-dependent.
- KV7.1 is functionally expressed in neonatal pig renal vascular smooth muscle cells.
- SMC KV7.1 plays a role in neonatal renal autoregulation, not basal vascular tone.
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