Individuals with spinal cord injuries (SCl) above T6 experience episodic bouts of life-threatening hypertension termed autonomic dysreflexia (AD). If not treated promptly, the hypertension may produce cerebral and sub-arachnoid hemorrhage, seizures, ventricular arrhythmias, renal failure, and may lead to death. Enhanced vasoconstrictor responses to sympathetic stimulation may account for some, if not the majority, of the pressor response of AD. Sympathetic stimulation causes vasoconstriction by co-releasing norepinephrine onto alpha-adrenergic receptors, neuropeptide Y (NPY) onto Y1 receptors and ATP onto P2x purinoreceptors. To date, only the role of alpha-adrenergic receptor hyper-responsiveness in mediating AD has been investigated. This is surprising since it is well documented that the pattern of sympathetic nerve activity determines the relative contribution that each co-transmitter makes to vasoconstriction. Importantly, SCI alters the pattern of sympathetic activity. Furthermore, the influence of SCI on endothelium-dependent vasodilation and buffering of sympathetically mediated vasoconstriction has not been investigated. Importantly, endothelial derived nitric oxide and vasodilatory prostacyclin buffers the vasoconstrictor response to sympathetic stimulation. Finally, measures designed to reduce vasoconstrictor hyper-responsiveness have not been examined. A single bout of dynamic exercise attenuates the post-exercise vasoconstrictor response to sympathetic stimulation. Thus, the ability of vessels to respond to a change in sympathetic nerve activity after exercise is attenuated. Therefore, this proposal is designed to assess the role of sympathetic co-transmitters, endothelial function, and molecular adaptations on vasoconstrictor responses in intact and paraplegic rats. In addition, the effects of a single bout of exercise on vasoconstrictor responses will be examined. The clinical significance of the post-exercise modulation of vascular function will be determined by the evaluating the cardiovascular and sympathetic nerve responses to colon distension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL074122-03
Application #
6909813
Study Section
Respiratory Physiology Study Section (RESP)
Program Officer
Ershow, Abby
Project Start
2003-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$377,500
Indirect Cost
Name
Wayne State University
Department
Physiology
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Lujan, Heidi L; Palani, Gurunanthan; DiCarlo, Stephen E (2010) Structural neuroplasticity following T5 spinal cord transection: increased cardiac sympathetic innervation density and SPN arborization. Am J Physiol Regul Integr Comp Physiol 299:R985-95
Drummond, Micah J; Glynn, Erin L; Lujan, Heidi L et al. (2008) Gene and protein expression associated with protein synthesis and breakdown in paraplegic skeletal muscle. Muscle Nerve 37:505-13
Dreyer, Hans C; Glynn, Erin L; Lujan, Heidi L et al. (2008) Chronic paraplegia-induced muscle atrophy downregulates the mTOR/S6K1 signaling pathway. J Appl Physiol 104:27-33
Glynn, Erin L; Lujan, Heidi L; Kramer, Victoria J et al. (2008) A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle. Appl Physiol Nutr Metab 33:93-101
Lujan, Heidi L; Dicarlo, Stephen E (2008) Sex differences to myocardial ischemia and beta-adrenergic receptor blockade in conscious rats. Am J Physiol Heart Circ Physiol 294:H1523-9
Lujan, Heidi L; DiCarlo, Stephen E (2007) T5 spinal cord transection increases susceptibility to reperfusion-induced ventricular tachycardia by enhancing sympathetic activity in conscious rats. Am J Physiol Heart Circ Physiol 293:H3333-9
Lujan, Heidi L; Kramer, Victoria J; DiCarlo, Stephen E (2007) Sex influences the susceptibility to reperfusion-induced sustained ventricular tachycardia and beta-adrenergic receptor blockade in conscious rats. Am J Physiol Heart Circ Physiol 293:H2799-808
Llewellyn-Smith, Ida J; Martin, Carolyn L; Fenwick, Natalie M et al. (2007) VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord. J Comp Neurol 503:741-67
Lujan, Heidi L; Kramer, Victoria J; DiCarlo, Stephen E (2007) Electroacupuncture decreases the susceptibility to ventricular tachycardia in conscious rats by reducing cardiac metabolic demand. Am J Physiol Heart Circ Physiol 292:H2550-5
Collins, Heidi L; Rodenbaugh, David W; DiCarlo, Stephen E (2006) Spinal cord injury alters cardiac electrophysiology and increases the susceptibility to ventricular arrhythmias. Prog Brain Res 152:275-88

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