# Small molecule NO precursors as a bioactive source of NO in vasodilation and angiogenesis

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $449,839

## Abstract

This application is conceived on the premise that in certain diseases, e.g. peripheral artery
disease (PAD), traditional therapies are ineffective in the treatment of symptoms and related
morbidities. PAD currently impacts over 8 million Americans and will affect many more as our
nation ages. The health care costs to treat subjects are significant ($4 billion annually by
Medicare), with most patients requiring numerous endovascular and surgical procedures
including amputation. Medical therapy has failed to impact the trend in this cost and efficacy curve.
This proposal seeks to change this paradigm by recognizing the endothelial dysfunction attributed
to PAD prevents proper blood flow recovery (vasodilation and angiogenesis) because the
production of nitric oxide through its cognate enzyme nitric oxide synthase is impaired. We have
found nitric oxide (NO) precursors in blood and tissues which are stimulated by red light energy
to release NO and produce a stable NO bound vasodilator. Furthermore, the release of this
autocrine factor dilates arteries/arterioles in the absence of nitric oxide synthase (NOS). The
actions of red light are clinically relevant, as we have identified significant elevations in blood flow
when the gastrocnemius muscle of healthy subjects and patients with PAD are exposed to red
light. The approach in this application will be to assess the impact of these iron and thiol based
NO precursors using biochemical and cell culture techniques, optimize light delivery in a murine
model of subacute hindlimb ischemia (to mimic clinical PAD), and confirm our findings in human
subjects with PAD. We expect the data collected will identify the mechanisms by which NO
intracellular NO precursor molecules can be increased, improve endothelial dysfunction and
enhance limb perfusion.

## Key facts

- **NIH application ID:** 10166902
- **Project number:** 5R01HL139557-03
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Nicole Lohr
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $449,839
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166902

## Citation

> US National Institutes of Health, RePORTER application 10166902, Small molecule NO precursors as a bioactive source of NO in vasodilation and angiogenesis (5R01HL139557-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10166902. Licensed CC0.

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