Sleep-disordered breathing has emerged as a risk factor for many forms of cardiovascular disease; however, the underlying mechanisms are incompletely understood. Our goal is to determine whether sleep-disordered breathing alters structure and function of resistance vessels in the cerebral and skeletal muscle circulations. We will investigate the time course and reversibility of these vascular alterations and examine the causative roles played by oxidant stress and sympathetic neural activation. Humans subjects with obstructive sleep apnea and rats exposed to chronic intermittent hypoxia (CIH) will be studied to address 4 specific aims.
In Aim 1, we will perform in vitro studies of isolated, perfused middle cerebral and gracilis arteries of the rat to determine the time course and potential for reversibility of CIH-induced impairments in vascular structure and function. In addition, we will assess the roles of sleep fragmentation and cyclic dexoygenation/reoxygenation in causing CIH-induced alterations in vascular function.
In Aim 2, we will use similar in vitro methods to determine whether oxidant stress contributes importantly to CIH-induced vascular dysfunction.
In Aim 3, we use chemical and surgical sympathectomy and angiotensin II receptor blockade to assess the role of the sympathetic nervous system causing CIH-induced vascular dysfunction.
In Aim 4, we will explore the functional consequences of CIH-induced vascular dysfunction in humans by assessing vasodilatory responses to acute episodes of hypoxia and hypercapnia before and after treatment of obstructive sleep apnea. The results of these experiments will further define the pathogenetic link between sleep-disordered breathing and cardiovascular disease and may lead to the development of a more rational approach to therapy for this common clinical condition.
| Marcus, Noah J; Philippi, Nathan R; Bird, Cynthia E et al. (2012) Effect of AT1 receptor blockade on intermittent hypoxia-induced endothelial dysfunction. Respir Physiol Neurobiol 183:67-74 |
| Dopp, John M; Philippi, Nathan R; Marcus, Noah J et al. (2011) Xanthine oxidase inhibition attenuates endothelial dysfunction caused by chronic intermittent hypoxia in rats. Respiration 82:458-67 |
| Philippi, Nathan R; Bird, Cynthia E; Marcus, Noah J et al. (2010) Time course of intermittent hypoxia-induced impairments in resistance artery structure and function. Respir Physiol Neurobiol 170:157-63 |
| Dempsey, Jerome A; Veasey, Sigrid C; Morgan, Barbara J et al. (2010) Pathophysiology of sleep apnea. Physiol Rev 90:47-112 |
| Marcus, Noah J; Li, Yu-Long; Bird, Cynthia E et al. (2010) Chronic intermittent hypoxia augments chemoreflex control of sympathetic activity: role of the angiotensin II type 1 receptor. Respir Physiol Neurobiol 171:36-45 |
| Reichmuth, Kevin J; Dopp, John M; Barczi, Steven R et al. (2009) Impaired vascular regulation in patients with obstructive sleep apnea: effects of continuous positive airway pressure treatment. Am J Respir Crit Care Med 180:1143-50 |
| Bautista, Leonelo E; Stein, James H; Morgan, Barbara J et al. (2009) Association of blood and hair mercury with blood pressure and vascular reactivity. WMJ 108:250-2 |
| Marcus, Noah J; Olson Jr, E Burt; Bird, Cynthia E et al. (2009) Time-dependent adaptation in the hemodynamic response to hypoxia. Respir Physiol Neurobiol 165:90-6 |
| Leinum, Corey J; Dopp, John M; Morgan, Barbara J (2009) Sleep-disordered breathing and obesity: pathophysiology, complications, and treatment. Nutr Clin Pract 24:675-87 |
| Dopp, John M; Reichmuth, Kevin J; Morgan, Barbara J (2007) Obstructive sleep apnea and hypertension: mechanisms, evaluation, and management. Curr Hypertens Rep 9:529-34 |
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