This Program Project Grant focuses on Integrative Neurobiology of Cardiovascular Regulation. Now in its 36th year, it represents the major scientific emphasis of the Cardiovascular Research Center at Iowa. The strength of this competitive renewal is based on the cohesion and synergy of its senior leadership, its constant evolution in concepts and approaches with new investigative talent, and the continuum of the effort from discovery of mechanisms to their translation into disease states in animal models and humans. The functional integration of the three components of autonomic control of the circulation is represented in four projects. Project I: Neural Processing of the Lamina Terminalis and Long-Term Regulation of Blood Pressure (Johnson, Hay) will identify molecular determinants of activation of central neurons in the lamina terminalis - a key regulatory site for the initiation of neurohumoral drive. Project II - Renin-Angiotensin-Aldosterone System and Sympathetic Activation in Obesity-Hypertension (Haynes, Mark, Rahmouni) will address the coupling of the two major components of neurohumoral drive to the cardiovascular system, namely the sympathetic nervous system and the renal-angiotensin-aldosterone system in as determinants of hypertension in obese humans. Project III - Cardiovascular Sensory Transduction by Acid Sensing Ion Channels (Abboud, Benson, Welsh) will address the molecular sensors involved in mechanotransduction of baroreceptors and chemoreceptor activation that maintain an autonomic balance of the cardiovascular system that is essential for survival in cardiovascular disease. Project IV - ROS Signaling in Baroreceptor and Sympathetic Neurons in Normal and Heart Failure States (Chapleau, Anderson, Weiss) will focus on ROS as a physiologic and pathologic modulator of afferent (baroreceptors) and efferent (sympathetic) neural activation, with fatal causal implications in a new model of heart failure. The molecular targets in the five projects also reflect a level of integration similar to the functional ones. There is convergence from the neurobiology of cardiovascular sensory organs (e.g. baro-chemo-receptors;circumventricular organs);to neurohumoral signaling molecules (angiotensin, aldosterone);to transmembrane receptors, reactive oxygen species, molecular transducters, and channels/channel protein. The Administration Core, the Vector Core and Animal Models Core are already providing invaluable service to the existing programs. The technical approaches are state-of-the-art, the animal models are well established, and the relevance to morbid conditions and fatal diseases such as heart failure, myocardial infarction, hypertension, atherosclerosis, dysautonomia, and obesity is direct. Common threads create the intellectual fabric of this program where the integrated outcome will be far greater than the sum of the components.

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
Thrasher, Terry N
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Internal Medicine/Medicine
Schools of Medicine
Iowa City
United States
Zip Code
Li, You; Shen, Xiao Z; Li, Liang et al. (2017) Brain Transforming Growth Factor-? Resists Hypertension Via Regulating Microglial Activation. Stroke 48:2557-2564
Pierce, Gary L; Kalil, Graziela Z; Ajibewa, Tiwaloluwa et al. (2017) Anxiety independently contributes to elevated inflammation in humans with obesity. Obesity (Silver Spring) 25:286-289
DuBose, Lyndsey E; Voss, Michelle W; Weng, Timothy B et al. (2017) Carotid ?-stiffness index is associated with slower processing speed but not working memory or white matter integrity in healthy middle-aged/older adults. J Appl Physiol (1985) 122:868-876
Shaffer Jr, Joseph J; Johnson, Casey P; Fiedorowicz, Jess G et al. (2017) Impaired sensory processing measured by functional MRI in Bipolar disorder manic and depressed mood states. Brain Imaging Behav :
Singh, Madhu V (2017) Toll-Like Receptors, Hypertension, and an Antimalarial Drug. Am J Hypertens 30:118-119
Konstam, Marvin A; Abboud, Fran├žois M (2017) Ejection Fraction: Misunderstood and Overrated (Changing the Paradigm in Categorizing Heart Failure). Circulation 135:717-719
Xue, Baojian; Yin, Haifeng; Guo, Fang et al. (2017) Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring. Hypertension 69:669-677
Singh, Madhu V; Cicha, Michael Z; Kumar, Santosh et al. (2017) Abnormal CD161+ immune cells and retinoic acid receptor-related orphan receptor ?t-mediate enhanced IL-17F expression in the setting of genetic hypertension. J Allergy Clin Immunol 140:809-821.e3
Wang, Runping; Lu, Yongjun; Gunasekar, Susheel et al. (2017) The volume-regulated anion channel (LRRC8) in nodose neurons is sensitive to acidic pH. JCI Insight 2:e90632
Pierce, Gary L (2017) Mechanisms and Subclinical Consequences of Aortic Stiffness. Hypertension 70:848-853

Showing the most recent 10 out of 155 publications