This is a resubmission of a program project grant to the NHLBI by {four} investigators located within the College of Medicine of the Pennsylvania State University in Hershey, Pennsylvania. All investigators are highly productive scientists. All project 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 {peripheral arterial disease (PAD) accentuates autonomic reflex responses. Two models of limb ischemia will be employed: a) PAD in human subjects (Projects 1 and 4);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 first 5 year funding period;and 4) many of the ideas and concepts proposed are a direct result of previous collaborations 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 Penn State General Clinical Research Center (GCRC) since 1996, and PD of a PPG since 2004. In Project 1, Dr. Sinoway will examine the role the exercise pressor reflex (EPR) {plays in regulating blood pressure during muscular activity in patients with PAD.} He will examine the role oxidative stress plays in altering reflex effects in PAD patients. In Project 2, Dr. Li will determine if hindlimb arterial occlusion (rat model) leads to upregulation of P2X, TRPV1 and ASIC channels in dorsal root ganglion (DRG) neurons. Dr. Li will also examine the role nerve growth factor (NGF) plays in this response. In Project 3, Dr. Kaufman will examine group III and IV muscle afferent discharge {during contraction in rats with the hindlimb arterial occlusion model.} In Project 4, Dr. Leuenberger will examine the role intermittent hypoxia, a potent oxidative stress, plays in altering sympathetic reflexes and vasodilator responsiveness in {normal humans and those with diseases characterized by oxidative stress including PAD. Two cores are proposed: 1) Core A will be administrative;and 2) Core B will be a human physiology core.

Public Health Relevance

In PAD, autonomic reflex and vascular adjustments are understudied and of major clinical significance. PAD is common and lethal. Moreover, it is often a harbinger of other life threatening diseases (coronary and cerebral atherosclerosis). In severe PAD, blood pressure rises dramatically with wall

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Maric-Bilkan, Christine
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Pennsylvania State University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Clark, Christine M; Monahan, Kevin D; Drew, Rachel C (2018) Omega-3 polyunsaturated fatty acid supplementation reduces blood pressure but not renal vasoconstrictor response to orthostatic stress in healthy older adults. Physiol Rep 6:e13674
Drew, Rachel C; Blaha, Cheryl A; Herr, Michael D et al. (2017) Muscle mechanoreflex activation via passive calf stretch causes renal vasoconstriction in healthy humans. Am J Physiol Regul Integr Comp Physiol 312:R956-R964
Cui, Jian; Boehmer, John; Blaha, Cheryl et al. (2017) Muscle sympathetic nerve activity response to heat stress is attenuated in chronic heart failure patients. Am J Physiol Regul Integr Comp Physiol 312:R873-R882
Drew, Rachel C (2017) Baroreflex and neurovascular responses to skeletal muscle mechanoreflex activation in humans: an exercise in integrative physiology. Am J Physiol Regul Integr Comp Physiol 313:R654-R659
Xing, Jihong; Li, Jianhua (2017) TRPA1 Function in Skeletal Muscle Sensory Neurons Following Femoral Artery Occlusion. Cell Physiol Biochem 42:2307-2317
Li, Zhijun; Muller, Matthew D; Wang, Jianli et al. (2017) Dynamic characteristics of T2*-weighted signal in calf muscles of peripheral artery disease during low-intensity exercise. J Magn Reson Imaging 46:40-48
Ross, Amanda J; Gao, Zhaohui; Luck, Jonathan Carter et al. (2017) Coronary Exercise Hyperemia Is Impaired in Patients with Peripheral Arterial Disease. Ann Vasc Surg 38:260-267
Luck, J Carter; Miller, Amanda J; Aziz, Faisal et al. (2017) Blood pressure and calf muscle oxygen extraction during plantar flexion exercise in peripheral artery disease. J Appl Physiol (1985) 123:2-10
Xing, Jihong; Li, Jianhua (2017) Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion. Cell Physiol Biochem 44:163-171
Xing, Jihong; Li, Jianhua (2016) The Role Played by Adenosine in Modulating Reflex Sympathetic and Pressor Responses Evoked by Stimulation of TRPV1 in Muscle Afferents. Cell Physiol Biochem 40:39-48

Showing the most recent 10 out of 73 publications