# Acute and Chronic Afferent Engagement: Sympathetic and End Organ Responses

> **NIH NIH P01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $1,870,043

## Abstract

PROJECT SUMMARY/ABSTRACT – OVERALL
This is a new application of a program project grant to the NHLBI by three investigators located within the
College of Medicine of the Pennsylvania State University in Hershey, Pennsylvania. All investigators are highly
productive scientists. All Project and Core Leaders are collaborative and all will greatly benefit from this
program. We believe this application fulfills the criteria for a PPG because: 1) there is a unifying theme namely
that the exercise pressor reflex (EPR) is accentuated in peripheral artery disease (PAD) and this accentuation
has significant cardiovascular consequences. Two models of limb ischemia will be employed to explore this
reflex: (a) PAD in human subjects (Project 1); and (b) hindlimb arterial occlusion in rats (Projects 2 and 3); 2)
conceptual synergy exists between the projects that will lead to important advances in cardiovascular
physiology and pathophysiology; 3) this PPG has broadly defined goals that can be accomplished within the 5
year funding period; and 4) many of the ideas and concepts proposed are a direct result of previous
interactions between the project leaders. Dr. Sinoway will be the PPG Program Director (PD). He has
substantial scientific and administrative experience, serving as the PD of the NIH funded Clinical and
Translational Science Institute at Penn State, and PD of a PPG from 2004 to 2016. In Project 1, Dr. Sinoway
will examine the cardiovascular consequences of an accentuated exercise pressor reflex in human subjects
with PAD and intermittent claudication. He will examine the impact the accentuated reflex has on the peripheral
and cardiac circulations. In Project 2, Dr. Li will examine the role pro-inflammatory cytokines play in altering
the blood pressure response to hindlimb contraction after hindlimb arterial occlusion. He will also examine how
pro-inflammatory cytokines alter signal transduction in DRG neurons of these animals. In Project 3, Dr.
Kaufman will examine the role EP4, ASIC3 and P2X3 receptors on DRG neurons play in accentuating the
pressor reflex to hindlimb contraction in rodents with hindlimb arterial occlusion. Two core laboratories are
proposed; an Administrative (Core A) that will oversee all administrative functions and a Transfection Core
Laboratory (Core B) that will design effective siRNA sequences and provide cDNA clones that code for these
`short hairpin' nucleotide sequences, perform the in vivo and in vitro transfection of DRG (L4-L5) and
gastrocnemius muscle, and verify protein knockdown employing quantitative RT-PCR (mRNA levels) and
Western blotting (protein quantification).

## Key facts

- **NIH application ID:** 9857642
- **Project number:** 5P01HL134609-04
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Lawrence I Sinoway
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,870,043
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857642

## Citation

> US National Institutes of Health, RePORTER application 9857642, Acute and Chronic Afferent Engagement: Sympathetic and End Organ Responses (5P01HL134609-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857642. Licensed CC0.

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