The Experimental Neurogenic Hypertension Program is a long-standing multidisciplinary research program focusing on the reciprocal interaction between the brain and the circulatory system. The central theme of the program is that, while the brain exerts a powerful influence over the circulation, the circulatory system, in turn, can have profound effects on the brain. Alterations of this delicate balance can produce hypertension and disrupt brain function. The present renewal application is organized in three Projects supported by three Cores. The Projects address diverse aspects of the central theme, but share a common focus on angiotensin II and its recently-recognized signaling system NAD(P)H oxidase. Project 1 investigates the mechanisms by which angiotensin II-induced hypertension impairs critical homeostatic mechanisms that provide blood flow to active brain regions, and examines on the role of NAD(P)H oxidase in the cerebrovascular dysfunction. Project 2 focuses on angiotensin receptors in the nucleus of the solitary tract, their relationships to catecholaminergic receptors and NAD(P)H oxidase subunits, and the changes in their subcellular targeting brought about by chronic intermittent hypoxia or angiotensin II-induced hypertension. Project 3 examines the cellular mechanisms underlying the effects of estrogens, androgens and progestins on neurons in the rostroventrolateral medulla, focusing on angiotensin receptors, and NAD(P)H oxidase subunits. The Projects are supported by an Administrative Core, a Molecular Biology-Mouse Core and a Neuroanatomy-Imaging Core. All Projects combine neuroanatomical, neurophysiological and molecular approaches to test the proposed hypothesis. The Projects build on each other's strengths so that the scientific output of one Project interacts synergistically with the research proposed in other Projects. Thus, the collective scientific outcome of the Program is anticipated to be greater than the sum of its individual components. The proposed studies are relevant to human diseases, such as hypertension-induced cognitive dysfunction, cardiovascular complications of sleep apnea, and cardiovascular diseases in post-menopausal women.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL018974-26A1
Application #
6762286
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Velletri, Paul A
Project Start
1998-07-01
Project End
2009-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
26
Fiscal Year
2004
Total Cost
$1,666,670
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Neurology
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Glass, Michael J; Chan, June; Pickel, Virginia M (2017) Ultrastructural characterization of tumor necrosis factor alpha receptor type 1 distribution in the hypothalamic paraventricular nucleus of the mouse. Neuroscience 352:262-272
Takahashi, Reisuke H; Capetillo-Zarate, Estibaliz; Lin, Michael T et al. (2013) Accumulation of intraneuronal ýý-amyloid 42 peptides is associated with early changes in microtubule-associated protein 2 in neurites and synapses. PLoS One 8:e51965
Misono, K; Lessard, A (2012) Apomorphine-evoked redistribution of neurokinin-3 receptors in dopaminergic dendrites and neuronal nuclei of the rat ventral tegmental area. Neuroscience 203:27-38
Van Kempen, Tracey A; Milner, Teresa A; Waters, Elizabeth M (2011) Accelerated ovarian failure: a novel, chemically induced animal model of menopause. Brain Res 1379:176-87
Williams, Tanya J; Akama, Keith T; Knudsen, Margarete G et al. (2011) Ovarian hormones influence corticotropin releasing factor receptor colocalization with delta opioid receptors in CA1 pyramidal cell dendrites. Exp Neurol 230:186-96
Williams, T J; Milner, T A (2011) Delta opioid receptors colocalize with corticotropin releasing factor in hippocampal interneurons. Neuroscience 179:9-22
Williams, Tanya J; Torres-Reveron, Annelyn; Chapleau, Jeanette D et al. (2011) Hormonal regulation of delta opioid receptor immunoreactivity in interneurons and pyramidal cells in the rat hippocampus. Neurobiol Learn Mem 95:206-20
Spencer-Segal, Joanna L; Waters, Elizabeth M; Bath, Kevin G et al. (2011) Distribution of phosphorylated TrkB receptor in the mouse hippocampal formation depends on sex and estrous cycle stage. J Neurosci 31:6780-90
Williams, Tanya J; Mitterling, Katherine L; Thompson, Louisa I et al. (2011) Age- and hormone-regulation of opioid peptides and synaptic proteins in the rat dorsal hippocampal formation. Brain Res 1379:71-85
Takahashi, Reisuke H; Capetillo-Zarate, Estibaliz; Lin, Michael T et al. (2010) Co-occurrence of Alzheimer's disease ß-amyloid and ? pathologies at synapses. Neurobiol Aging 31:1145-52

Showing the most recent 10 out of 294 publications