Neonatal renal vasoregulation by voltage-gated potassium channels

Project: Research

Investigators

  • Dieniffer Peixoto-neves (PI)

Description

In resistance size microvessels, an elevation in perfusion pressure stimulates vascular smooth muscle cell plasma membrane depolarization leading to vasoconstriction; whereas, a decrease in perfusion pressure elicits vasodilation via smooth muscle cell hyperpolarization. This process termed the 'myogenic response' is significant as it autoregulates renal blood flow and glomerular filtration rate, and serves to protect the kidneys from injury. Despite the high risk of developing acute kidney injury due to adverse perinatal conditions, such as sepsis, mechanisms that control renal vascular reactivity in neonates is poorly understood. Our recent findings indicate that although the arterial pressure is low, renal myogenic vasoconstriction is fully functional in neonatal pigs. Whether neonatal renal blood flow autoregulates in response to a step decrease in arterial pressure is unclear. Thus, we propose a central hypothesis that activation of renal vascular Kv7.1 channels and resultant membrane hyperpolarization and vasodilation underlie neonatal renal vasoregulation induced by a step decrease in arterial pressure. To address this concept, two specific aims will be studied in neonatal pigs: 1) to investigate whether that Kv7.1 channels contribute to myogenic vasodilation mechanisms of neonatal renal autoregulation; 2) to study the hypothesis that that KV7.1 channels are required to maintain renal autoregulation during the early hyperdynamic phase of neonatal sepsis. We anticipate that this project will accrue mechanistic data that will not only increase the knowledge of the physiology and pathophysiology of neonatal renal microvessels, but may lead to elucidation of potential therapeutic targets for renal vasculopathy in newborns.
Award amount$106,532.00
Award date07/01/2018
Program typePostdoctoral Fellowship
Award ID18POST34030240
Effective start/end date07/01/201806/30/2020
StatusFinished