Understanding Salt-Sensitive Hypertension: Spinal Regulation of Sympathetic Nerve Activity and Blood Pressure Under Conditions of Increased Plasma Osmolality
Medical Research Manager, NAMSA
Undergraduate Institution and Major/Degree:
Carleton College, BA, Chemistry, 2004
Medical Research Manager, NAMSA
John Osborn, Ph.D
The primary research focus on neural mechanisms of hypertension over the last 40 years has been on neural networks in the brain. Progress in this area has been slow and the ability to translate this knowledge into development of novel therapies has proven to be extremely challenging. In contrast, very little research on spinal level control of arterial pressure has been done, particularly in conscious animals. My thesis focuses on neural control of arterial pressure at the level of the spinal cord under conditions of increased plasma osmolality. The goal is to identify spinal neurotransmitter/receptor systems and the sympathetic nerves that mediate increases in arterial pressure to osmotic stress in conscious, unrestrained rats. The long-term application of this work would be to directly target the identified system to develop novel antihypertensive therapies.
My experiments investigate the role of two neurotransmitters, vasopressin and glutamate, in the spinal-level control of arterial pressure. To do this, indwelling intrathecal catheters are implanted to administer antagonists to the spinal cord region, and radiotelemetry transmitters are implanted for continuous monitoring of arterial pressure and heart rate. Additionally, regional sympathetic denervations are performed to identify the sympathetic nerves involved in the pressor responses to osmotic stress. We aim to elucidate the spinal pathways involved in elevating arterial pressure during acute intravenous hypertonic saline, 48-hour water deprivation, and the chronic DOCA-salt model of hypertension.
- Alice Larson
- William Engeland
- John Osborn
- Cathy Kotz
Courses Taken Beyond the Core Courses:
- GRAD 8101 - Teaching in Higher Education
- HSL 5101 - Human Physiology
- NSU 5667 - Neurobiology in Disease
- PHM 8120 - Readings in CNS Drug Delivery
- PHM 8481 - Advanced Neuropharmaceutics
- PHSL 5510 - Adv Cardiac Physiology
Conferences Attended and Presentations:
- Experimental Biology annual meeting: 2008-2011
- FASEB Summer Conference - Neural Mechanisms in Cardiovascular Regulation: Saxtons River, VT, 2010
- Cardiovascular Control Conference: Mahabalipuram, India, 2008
- Poster Presentations: Veitenheimer, B and Osborn, J. Role of Spinal Vasopressin V1a Receptors in Mediating Mineralocorticoid-Salt Hypertension in Conscious Rats. Experimental Biology, 2008 – San Diego, CA
- Veitenheimer, B and Osborn, J. Arterial Pressure Rises During Chronic Increases in Osmolality: Role of Spinal Vasopressin V1a Receptors.
2nd Cardiovascular Control Conference, 2008 – Mahabalipuram, India
- Veitenheimer B, Guzman PA, Osborn J Characterization of the Cardiovascular Responses to Intrathecal Administration of Angiotensin II (AngII) in Conscious Rats. Experimental Biology, 2009 – New Orleans, LA
- John Osborn - Advisor
- Bill Engeland - Chair
- Scott O'Grady
- Martin Wessendorf
- Chris Honda
Selected Publications and Presentations:
- Fargali S, Garcia AL, Sadahiro M, Jiang C, Janssen WG, Lin WJ, Cogliani V, Elste A, Mortillo S, Cero C, Veitenheimer B, Graiani G, Pasinetti GM, Mahata SK, Osborn JW, Huntley GW, Phillips GR, Benson DL, Bartolomucci A, Salton SR. The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure. FASEB J. 2014;28(5):2120-33.
- Veitenheimer B, Osborn JW. Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats. Am J Physiol Heart Circ Physiol. 2013;304(2):H303-10.
- Veitenheimer BJ, Engeland WC, Guzman PA, Fink GD, Osborn JW. Effect of global and regional sympathetic blockade on arterial pressure during water deprivation in conscious rats. Am J Physiol Heart Circ Physiol. 2012;303(8):H1022-34
- Veitenheimer B, Osborn JW. Role of spinal V1a receptors in regulation of arterial pressure during acute and chronic osmotic stress. Am J Physiol Regul Integr Comp Physiol. 2011 300:R460-469, 2011.
- Veitenheimer, B and Osborn, J. Intrathecal Administration of a V1a Antagonist has No Effect on Arterial Pressure in Conscious Rats under Acute or Chronic Osmotic Stress FASEB Summer Conference - Neural Mechanisms in Cardiovascular Regulation, 2010 – Saxtons River, VT
Awards and Honors:
- Stark Travel Award, 2008
- University of Minnesota Graduate School Fellowship: 2006-2008
- American Physiological Society: 2008 - current