The baroreceptor (BR) activity transmitted to the central nervous system is determined not only by the mechanoelectrical transducing channels but also by various voltage-gated channels that influence membrane excitability of BR neurons. Hypothesis #1: The important paracrine factors prostacyclin (PGI/2) and nitric oxide (NO) directly influence excitability of BR neurons through modulation of voltage-gated K+ and Na+ channels. Effects of PGI/2 and No on membrane potential, spike firing properties, and K+ and Na+ currents of isolated BR neurons in culture will be demonstrated using patch-clamp techniques. Experiments will define the intracellular signal transduction pathways and mechanisms by which PGI/2 and NO influence channel activity. Hypothesis #2: PGI/2 and NO function as autocrine factors produced endogenously in response to mechanical deformation and consequently modulate excitability and mechanosensitivity of the BR neurons. Release of PGI2 and NO from isolated neurons will be measured and their impact on excitability evaluated by pharmacological inhibitors and antagonists. The influence of expression of PGH and NO synthases within individual BR neurons and effects of changing expression using gene transfer on mechano-sensitivity will be investigated. Hypothesis #3: Intracellular generation of reactive oxygen species (ROS) significantly modulates excitability of BR neurons by altering K+ and Na+ currents. Effects of ROS on excitability and K+ and Na+ currently will be demonstrated and the intracellular mechanisms defined. Prolonged oxidative stress will be induced by incubation of BR neurons with oxidized LDL and the impact on membrane excitability and K+ and Na+ currents investigated. The in vivo relevance of the results obtained from isolated BR neurons will be confirmed, when possible, in experiments using the isolated carotid sinus-BR preparation.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Iowa City
United States
Zip Code
Kopf, Phillip G; Phelps, Laura E; Schupbach, Chad D et al. (2018) Differential effects of long-term slow-pressor and subpressor angiotensin II on contractile and relaxant reactivity of resistance versus conductance arteries. Physiol Rep 6:
Zhang, Yu-Ping; Huo, Yan-Li; Fang, Zhi-Qin et al. (2018) Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and sensitization of angiotensin II-induced hypertension in adult offspring. Am J Physiol Heart Circ Physiol 314:H1061-H1069
Johnson, Casey P; Christensen, Gary E; Fiedorowicz, Jess G et al. (2018) Alterations of the cerebellum and basal ganglia in bipolar disorder mood states detected by quantitative T1? mapping. Bipolar Disord 20:381-390
Hardy, Rachel N; Simsek, Zinar D; Curry, Brandon et al. (2018) Aging affects isoproterenol-induced water drinking, astrocyte density, and central neuronal activation in female Brown Norway rats. Physiol Behav 192:90-97
Lane-Cordova, Abbi D; Kalil, Graziela Z; Wagner, Christopher J et al. (2018) Hemoglobin A1c and C-reactive protein are independently associated with blunted nocturnal blood pressure dipping in obesity-related prediabetes. Hypertens Res 41:33-38
Larson, Robert A; Chapleau, Mark W (2018) Increased cardiac sympathetic activity: Cause or compensation in vasovagal syncope? Clin Auton Res 28:265-266
Tong, Brian; Abosi, Oluchi; Schmitz, Samantha et al. (2018) Bipolar disorder and related mood states are not associated with endothelial function of small arteries in adults without heart disease. Gen Hosp Psychiatry 51:36-40
Zeng, Wei-Zheng; Marshall, Kara L; Min, Soohong et al. (2018) PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science 362:464-467
DuBose, Lyndsey E; Boles Ponto, Laura L; Moser, David J et al. (2018) Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans. Hypertension 72:476-482
Holwerda, Seth W; Luehrs, Rachel E; Gremaud, Allene L et al. (2018) Relative burst amplitude of muscle sympathetic nerve activity is an indicator of altered sympathetic outflow in chronic anxiety. J Neurophysiol 120:11-22

Showing the most recent 10 out of 175 publications