Little is known about how long term occlusion of arterial blood flow to skeletal muscle affects the responses of thin fiber muscle afferents to static contraction. We are proposing to investigate the effects of femoral arterial occlusion on the responses of thin fiber afferents to static contraction of the triceps surae muscles in decerebrate rats. Femoral arterial occlusion will be induced for three periods of time, namely three minutes, 24 hours and 72 hours. The two latter periods are intended to simulate intermittent claudication in the humans, whereas the first is intended to serve as an indicator of short term arterial occlusion. In addition, the 24 and 72 hour periods will allow us to compare the effects of arterial occlusion on the responses of the afferents to contraction when there has been an increase in TRPVi receptors and presumably when there has not been an increase in these receptors (i.e., three minutes). There is substantial evidence that femoral arterial occlusion in rats simulates arterial blood flow to muscle in humans with intermittent claudication during both during rest and during exercise. We will pay particular attention to how arterial occlusion over time alters the responses of thin fiber afferents to static contraction. We will attempt to block pharmacologically the receptors on thin fiber muscle afferents to determine which ones are playing a functional role in causing the altered (and usually increased) responsiveness of the thin fiber afferents to contraction. These receptors include TRPVi, acid sensing ion channels (ASIC), and purinergic 2 receptors In addition we will attempt to determine the effect of tempol, and agent which reduces oxidative stress, on the thin fiber afferents responses to static contraction.

Public Health Relevance

When blood flow to the leg is blocked by fatty plaques, people experience painful sensations when attempting to exercise. The experiments proposed in this research unit will attempt to characterize the specific chemicals that evoke this sensation of pain during exercise. The information obtained from these proposed studies may allow the development of drugs that prevent these exercise-induced painful sensations.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL096570-03
Application #
8378537
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$355,149
Indirect Cost
$125,331
Name
Pennsylvania State University
Department
Type
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Muller, Matthew D; Li, Zhijun; Sica, Christopher T et al. (2016) Muscle oxygenation during dynamic plantar flexion exercise: combining BOLD MRI with traditional physiological measurements. Physiol Rep 4:
Cui, Jian; Blaha, Cheryl; Sinoway, Lawrence I (2016) Whole body heat stress attenuates the pressure response to muscle metaboreceptor stimulation in humans. J Appl Physiol (1985) 121:1178-1186
Li, Zhijun; Muller, Matthew D; Wang, Jianli et al. (2016) Dynamic characteristics of T2*-weighted signal in calf muscles of peripheral artery disease during low-intensity exercise. J Magn Reson Imaging :
Ross, Amanda J; Gao, Zhaohui; Luck, Jonathan Carter et al. (2016) Coronary Exercise Hyperemia Is Impaired in Patients with Peripheral Arterial Disease. Ann Vasc Surg :
Copp, Steven W; Kim, Joyce S; Ruiz-Velasco, Victor et al. (2016) The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in decerebrate rats. J Physiol 594:641-55
Clark, Christine M; Monahan, Kevin D; Drew, Rachel C (2016) Omega-3 polyunsaturated fatty acid supplementation attenuates blood pressure increase at onset of isometric handgrip exercise in healthy young and older humans. Physiol Rep 4:
Stone, Audrey J; Kaufman, Marc P (2015) The exercise pressor reflex and peripheral artery disease. Auton Neurosci 188:69-73
Clark, Christine M; Monahan, Kevin D; Drew, Rachel C (2015) Aging augments renal vasoconstrictor response to orthostatic stress in humans. Am J Physiol Regul Integr Comp Physiol 309:R1474-8
Copp, Steven W; Stone, Audrey J; Li, Jianhua et al. (2015) Role played by interleukin-6 in evoking the exercise pressor reflex in decerebrate rats: effect of femoral artery ligation. Am J Physiol Heart Circ Physiol 309:H166-73
Muller, Matthew D; Drew, Rachel C; Ross, Amanda J et al. (2015) Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease. Am J Physiol Heart Circ Physiol 309:H523-8

Showing the most recent 10 out of 64 publications