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TRPV4 channels contribute to renal myogenic response in neonatal pigs
Author(s) -
Soni Hitesh,
PeixotoNeves Dieniffer,
Adebiyi Adebowale
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.701.7
Subject(s) - myogenic contraction , autoregulation , trpv4 , vasoconstriction , transient receptor potential channel , medicine , endocrinology , microcirculation , cardiology , chemistry , blood pressure , receptor , smooth muscle
Myogenic response, a phenomenon in which resistance size arteries and arterioles swiftly constrict or dilate in response to acute elevation or reduction, respectively in intravascular pressure is a key component of renal blood flow (RBF) autoregulation mechanisms. Although it is well‐established that the renal system is functionally immature in newborns, renal autoregulation mechanisms in neonates remain poorly understood. In this study, we investigated the hypothesis that members of the transient receptor potential vanilloid (TRPV) channels are molecular components of myogenic response in newborns. We show that TRPV4 channels are predominantly expressed in neonatal pig preglomerular vascular smooth muscle cells (SMCs). Stretch‐induced intracellular Ca 2+ ([Ca 2+ ] i ) elevation in distal interlobular artery SMCs and vasoconstriction were diminished by selective TRPV4 channel blocker HC‐067047. HC‐067047 also inhibited pressure‐induced membrane depolarization, [Ca 2+ ] i elevation, and constriction in the microvessels. In anesthetized and mechanically ventilated neonatal pigs, step increases in arterial pressure up to 120 mmHg induced efficient autoregulation of RBF and cortical perfusion. Furthermore, intrarenal infusion of TRPV4 channel blockers HC‐067047 and RN‐1734 attenuated renal autoregulation in the pigs. These data suggest that renal myogenic autoregulation is functional in neonates. Our findings also indicate that TRPV4 channels are mechanosensors in neonatal pig preglomerular vascular SMCs, and contribute to renal myogenic autoregulation. Support or Funding Information NIH R01 DK101668