Sustained elevated blood pressure-hypertension is a prominent cause of morbidity and deaths throughout the world. Hypertension is associated with increased activity in the sympathetic nervous system resulting in constriction of blood vessels, increased heart contractility and retention of sodium and water. It is the central hypothesis of this project that veins and arteries are innervated by separate neurons in sympathetic ganglia and that alterations in properties of vein neurons contribute to venoconstriction in hypertension. In normotensive and DOCA-salt hypertensive rats we will compare the properties of identified arterial and venous neurons in the prevertebral sympathetic ganglia that innervate the splanchnic blood vessels and and determine their properties with respect to firing behavior, generation of reactive oxygen species and function of the norepinephrine uptake system. We also will compare the properties of prevertebral neurons to those in stellate ganglia that provide the sympathetic innervation to the heart and associated great vessels in the thorax. We will pursue the following specific aims. 1) Determine the localization and electrophysiologic characteristics of arterial and venous sympathetic neurons in the intact inferior mesenteric ganglion of the rat and characterize arterial and venous neurons in primary dissociated cell culture. 2) Determine the localization and regulation of ROS-generating enzymes within the arterial and venous neurons of celiac ganglia and within stellate ganglion neurons. 3) Determine the mechanisms of regulation of sympathetic neuron function by ETB receptors. 4) Compare the properties of celiac ganglion neurons (peripheral volume regulation) to those of stellate ganglion neurons (central volume regulation). Our long-term objective is to discover novel properties of the sympathetic nervous system that will be susceptible to treatment of human hypertension. LAY SUMMARY: High blood pressure is a major health problem. The sympathetic nervous system, the part of the nervous system that functions when the body is stressed, is hyperactive in hypertension. This overactivity is a cause of the disease and many of the bad effects that accompany it. This study tries to find out what malfunctions in the nerve cells that are outside the brain and spinal cord that innervate the arteries, veins and heart. We think that the nerves that innervate veins cause them to contract too much and this is one cause of high blood pressure. We hope to discover a treatment based on this idea.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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Michigan State University
East Lansing
United States
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Fernandes, Roxanne; Garver, Hannah; Harkema, Jack R et al. (2018) Sex Differences in Renal Inflammation and Injury in High-Fat Diet-Fed Dahl Salt-Sensitive Rats. Hypertension 72:e43-e52
Diaz-Otero, Janice Marie; Yen, Ting-Chieh; Fisher, Courtney et al. (2018) Mineralocorticoid Receptor Antagonism Improves Parenchymal Arteriole Dilation Via a TRPV4-Dependent Mechanism and Prevents Cognitive Dysfunction in Hypertension. Am J Physiol Heart Circ Physiol :
Jackson, William F; Boerman, Erika M (2018) Voltage-gated Ca2+ channel activity modulates smooth muscle cell calcium waves in hamster cremaster arterioles. Am J Physiol Heart Circ Physiol 315:H871-H878
Ahmad, Maleeha F; Ferland, David; Ayala-Lopez, Nadia et al. (2018) Perivascular Adipocytes Store Norepinephrine by Vesicular Transport. Arterioscler Thromb Vasc Biol :ATVBAHA118311720
Matin, Nusrat; Fisher, Courtney; Jackson, William F et al. (2018) Carotid artery stenosis in hypertensive rats impairs dilatory pathways in parenchymal arterioles. Am J Physiol Heart Circ Physiol 314:H122-H130
Kumar, Ramya K; Darios, Emma S; Burnett, Robert et al. (2018) Fenfluramine-induced PVAT-dependent contraction depends on norepinephrine and not serotonin. Pharmacol Res :
Thelen, Kyan; Watts, Stephanie W; Contreras, G Andres (2018) Adipogenic potential of perivascular adipose tissue preadipocytes is improved by coculture with primary adipocytes. Cytotechnology 70:1435-1445
Restini, Carolina Baraldi A; Ismail, Alex; Kumar, Ramya K et al. (2018) Renal perivascular adipose tissue: Form and function. Vascul Pharmacol 106:37-45
Jackson, William F (2018) KV channels and the regulation of vascular smooth muscle tone. Microcirculation 25:
Jackson, W F (2017) Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth. Adv Pharmacol 78:89-144

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