# Vascular ion channels and microcirculation in neonatal urinary tract obstruction

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $512,419

## Abstract

Urinary tract obstruction causes kidney injury, which, if left uncorrected, may lead to an irreversible renal loss
especially in infants. The pathophysiology of neonatal obstructive nephropathy has been a focus of considerable
research interests for decades, but significant gaps in understanding include vascular mechanisms that underlie
impairment of renal microcirculation. In the present application, we propose a novel concept that alterations of
newborn renal vascular resistance (RVR) and perfusion by acute ureteral obstruction are mediated by reactive
oxygen species-driven biosynthesis of peptidase endothelin-converting enzyme 1, which proteolytically processes
multiple renal big endothelins (ET1-3) to their vasoactive isoforms. ET-derived renal diacylglycerol (DAG) activates
renal vascular smooth muscle cell TRPC3 channels, leading to receptor-operated extracellular calcium entry,
prolonged vasoconstriction, RVR elevation, and hypoperfusion. To investigate these concepts, we will utilize
newborn pigs that are maintained under intensive care as a preclinical model for reversible urinary tract obstruction
in infants. These pigs and a novel TRPC3 knockout neonatal rat strain will be used to delineate calcium-dependent
signal transduction mechanisms in renal vascular smooth muscle cells that mediate 1) persistent hypoperfusion,
2) kidney injury, and 3) impaired myogenic renal autoregulation during and after acute urinary tract obstruction.
The proposed studies in this application will accrue mechanistic data that will not only improve our understanding
of neonatal renal vasculopathy but may lead to potential diagnostic markers or therapeutic targets for obstructive
renal insufficiency in newborns.

## Key facts

- **NIH application ID:** 9884233
- **Project number:** 1R01DK120595-01A1
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Adebowale Adebiyi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $512,419
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884233

## Citation

> US National Institutes of Health, RePORTER application 9884233, Vascular ion channels and microcirculation in neonatal urinary tract obstruction (1R01DK120595-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9884233. Licensed CC0.

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