Over 61 million Americans have some type of cardiovascular disease that is the leading cause of death in this country. Obesity and stress are two high risk factors for cardiovascular disease, especially hypertension. The melanocortins consist of a family of peptides derived from the common precursor pro-opiomelanocortin. These peptides include alpha-, beta-, and gamma-melanocyte stimulating and adrenocorticotropic hormones. Melanocortins have been implicated in feeding behavior, obesity and stress responses. For example, disruption of melanocortin containing neurons produces over eating and obesity. Mild stress has been reported to elicit over eating that can lead to obesity. In addition, melanocortin levels are elevated in stressful situations. These observations suggest that there may be a link between melanocortins, obesity, stress and cardiovascular disease. A prerequisite for understanding the role of melanocortins in cardiovascular function during obesity and stress is a clear understanding of the role of these peptides in the central cardiovascular regulation in normal conditions. The goal of the present project is to investigate the mechanism of cardiovascular actions of melanocortins in the nucleus tractus solitarius, caudal ventrolateral medullary depressor area, rostral ventrolateral medullary pressor area, the nucleus ambiguus, and the intermediolateral cell column of the thoraco-lumbar cord. These areas of the central nervous system are known to be involved in the regulation of cardiovascular function. Dense neuronal networks containing melanocortins have been identified in these regions. The hypothesis central to this project is that melanocortins excite neurons located in the medullo-spinal regions involved in cardiovascular regulation. The hypothesis is based on our preliminary results and published reports in which electrophysiological studies have shown excitation of neurons in specific regions of the brain. In each of the abovementioned regions, pharmacological and electrophysiological techniques will be used to investigate the mechanism of action of melanocortins. The information generated from this project will eventually be helpful in understanding the mechanisms connecting melanocortins, obesity, stress and cardiovascular disease. Furthermore, this information will help in developing novel and rational regimens of treatment for cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL076248-05
Application #
7369896
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Rabadan-Diehl, Cristina
Project Start
2004-03-05
Project End
2010-02-28
Budget Start
2008-03-01
Budget End
2010-02-28
Support Year
5
Fiscal Year
2008
Total Cost
$331,745
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107
Kawabe, Tetsuya; Iwasa, Masamitsu; Kawabe, Kazumi et al. (2016) Attenuation of angiotensin type 2 receptor function in the rostral ventrolateral medullary pressor area of the spontaneously hypertensive rat. Clin Exp Hypertens 38:209-17
Chitravanshi, Vineet C; Kawabe, Kazumi; Sapru, Hreday N (2015) GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited by chemical stimulation of the hypothalamic arcuate nucleus. Am J Physiol Heart Circ Physiol 309:H174-84
Kawabe, Tetsuya; Kawabe, Kazumi; Sapru, Hreday N (2014) Cardiovascular effect of angiotensin-(1-12) in the caudal ventrolateral medullary depressor area of the rat. Am J Physiol Heart Circ Physiol 306:H438-49
Chitravanshi, Vineet C; Kawabe, Kazumi; Sapru, Hreday N (2013) Mechanisms of cardiovascular actions of urocortins in the hypothalamic arcuate nucleus of the rat. Am J Physiol Heart Circ Physiol 305:H182-91
Iwasa, Masamitsu; Kawabe, Kazumi; Sapru, Hreday N (2013) Activation of melanocortin receptors in the intermediolateral cell column of the upper thoracic cord elicits tachycardia in the rat. Am J Physiol Heart Circ Physiol 305:H885-93
Kawabe, Tetsuya; Kawabe, Kazumi; Sapru, Hreday N (2013) Tonic ?-aminobutyric acid-ergic activity in the hypothalamic arcuate nucleus is attenuated in the spontaneously hypertensive rat. Hypertension 62:281-7
Arakawa, Hideki; Kawabe, Kazumi; Sapru, Hreday N (2013) Angiotensin-(1-12) in the rostral ventrolateral medullary pressor area of the rat elicits sympathoexcitatory responses. Exp Physiol 98:94-108
Sapru, Hreday N (2013) Role of the hypothalamic arcuate nucleus in cardiovascular regulation. Auton Neurosci 175:38-50
Kawabe, Tetsuya; Kawabe, Kazumi; Sapru, Hreday N (2012) Effect of barodenervation on cardiovascular responses elicited from the hypothalamic arcuate nucleus of the rat. PLoS One 7:e53111
Kawabe, Tetsuya; Kawabe, Kazumi; Sapru, Hreday N (2012) Cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus in the rat: role of the hypothalamic paraventricular nucleus. PLoS One 7:e45180

Showing the most recent 10 out of 32 publications