Cheryl M. Heesch, PhD
Research Interests
Neurohumoral control of circulation
Research Description
Neurohumoral control of the circulation; Hypertension; Central nervous system effects of ovarian hormones and progesterone metabolites on cardiovascular regulation.
Our laboratory's major focus is to understand how the central nervous system controls arterial blood pressure and how blood pressure is modulated in physiological and pathophysiological states. We evaluate basic mechanisms involved in central nervous system control of autonomic outputs, particularly in brainstem and forebrain regions which are critical for providing tonic drive to the sympathetic nervous system. We also study how ovarian hormones modulate these basic control mechanisms. Ongoing projects in the laboratory are focused on elucidating the role of central nervous system effects of ovarian hormones and progesterone metabolites in the alterations in control of sympathetic outflow associated with pregnancy. Once we understand the mechanisms for attenuated sympathoexcitation in normal pregnancy, it may be possible to determine the mechanisms for elevations of arterial blood pressure in hypertensive disorders, where sympathoexcitatory responses are exaggerated. Also, women are generally protected from heart disease and hypertension until the onset of menopause. Understanding the mechanisms for the protective role of ovarian hormones could have important implications for treatment and prevention of cardiovascular disorders. The possibility that a metabolite of progesterone, 3-alpha -OH-dihydroprogesterone, may play a major role in suppression of sympathoexcitatory responses is especially intriguing. 3-alpha -OH-dihydroprogesterone is the most potent endogenous positive modulator of central nervous system GABAA receptors and physiologically significant levels have been reported in the central nervous systems of both males and females. Both whole animal and molecular experimental approaches are used and include: 1) measurement of hemodynamics and sympathetic nerve activity; 2) CNS microinjection of putative transmitters and modulators; and 3) evaluation of neurotransmitter , neuromodulator, enzyme, and receptor expression in relevant brain regions using tissue micropunches or individually selected neurons (laser capture microscopy).
Professional Background
- Obtained PhD, University of Texas Health Science Center.
- Obtained BS, New Mexico State University.
Selected Publications
Hypoxia activates a neuropeptidergic pathway from the paraventricular nucleus of the hypothalamus to the nucleus tractus solitarii. Ruyle BC, Klutho PJ, Baines CP, Heesch CM, Hasser EM. Am J Physiol Regul Integr Comp Physiol. 2018 Sep 19. doi: 10.1152/ajpregu.00244.2018. [Epub ahead of print] PMID: 30230933
Loss of Female Sex Hormones Exacerbates Cerebrovascular and Cognitive Dysfunction in Aortic Banded Miniswine Through a Neuropeptide Y-Ca2+-Activated Potassium Channel-Nitric Oxide Mediated Mechanism. Olver TD, Hiemstra JA, Edwards JC, Schachtman TR, Heesch CM, Fadel PJ, Laughlin MH, Emter CA. J Am Heart Assoc. 2017 Oct 31;6(11). pii: e007409. doi: 10.1161/JAHA.117.007409. PMID: 29089345
Acute hypoxia activates neuroendocrine, but not presympathetic, neurons in the paraventricular nucleus of the hypothalamus: differential role of nitric oxide. Coldren KM, Li DP, Kline DD, Hasser EM, Heesch CM. Am J Physiol Regul Integr Comp Physiol. 2017 Jun 1;312(6):R982-R995. doi: 10.1152/ajpregu.00543.2016. Epub 2017 Apr 12. PMID: 28404583
Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats. Coldren KM, Brown R, Hasser EM, Heesch CM. Am J Physiol Regul Integr Comp Physiol. 2015 Dec 15;309(12):R1553-68. doi: 10.1152/ajpregu.00186.2015. Epub 2015 Sep 23. PMID: 26400184
Daniela Ostrowski, Allison C. Kleiber, Cheryl M. Heesch, David D. Kline, and Eileen M. Hasser. Nucleus tractus solitarii (nTS) is required for phrenic long term facilitation (pLTF) after acute intermittent hypoxia (AIH). FASEB J: 27: 697.16, 2013.
Kevin Max Coldren, Sean P. McCalmon, T. Luise King, David D. Kline, Eileen M. Hasser, and Cheryl M. Heesch. Acute hypoxia (AH) increases Fos-IR in nNOS and AVP cells in the paraventricular nucleus of the hypothalamus (PVN). FASEB J: 27: 697.26, 2013.
Stacy L. Barr, J. Glenn Phaup, David D. Kline, Eileen M. Hasser, and Cheryl M. Heesch. Chronic intermittent hypoxia (CIH, 3d) attenuates glutathione peroxidase expression (Gpx1) and function in the caudal nucleus tractus solitarii (cnTS). FASEB J: 27: 697.31, 2013.
T. Luise King, Cheryl M. Heesch, Brian C. Ruyle, David D Kline, and Eileen M Hasser. Catecholaminergic neurons projecting to the paraventricular nucleus (PVN) of the hypothalamus are essential for adjustments to respiratory challenges. FASEB J: 27: 697.20, 2013.
Allison Christine Kleiber, Daniela Ostrowski, David D Kline, Cheryl M Heesch and Eileen M Hasser. Nucleus tractus solitarii (nTS) reactive oxygen species (ROS) contribute) to acute intermittent hypoxia (AIH)-induced phrenic nerve long-term facilitation (pLTF). FASEB J: 27: 697.27, 2013.
Brian Christopher Ruyle, David D Kline, T Luise King, Cheryl M Heesch, and Eileen M Hasser, Activation of nucleus tractus solitarii (nTS) neurons that project to the rostral ventrolateral medulla (RVLM) or hypothalamic paraventricular nucleus (PVN): Role of acute hypoxia (AH). FASEB J: 27: 697.29, 2013.
Eileen M Hasser, Cheryl M Heesch, and David D Kline. Role of nucleus tractus solitarii (nTS) hydrogen sulfide (H2S) in hindlimb unloaded rats. FASEB J: 27: 697.30, 2013.
J. Glenn Phaup, Eileen M Hasser, and Cheryl M Heesch. The neurosteroid metabolite of progesterone, 3[alpha]-OH-dihydroprogesterone (3[apha]-OH-DHP), is required for attenuated baroreflex mediated sympathoexcitation in pregnancy. FASEB J: 27: 1118.38, 2013.
Manuscripts (Peer Reviewed)
Martins-Pinge MC, PJ Mueller, CM Foley, CM Heesch and EM Hasser. Regulation of arterial pressure by the paraventricular nucleus in conscious rats: Interactions among glutamate, GABA and nitric oxide. Frontiers in Physiology, 3: Article 490, Jan 2013. Doi: 10.3389/fphys.2012.00490.
King, TL, DD Kline, BC Ruyle, CM Heesch, EM Hasser. Acute systemic hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the caudal ventrolateral medulla. Amer. J. Physiol. (Regulatory, Integrative, & Comparative Physiol.), 305: R1112-R1123, 2013.
Owens, CM, F Marga, G Forgacs, CM Heesch. Biofabrication and testing of a fully cellular nerve graft. Biofabrication.5: (2013) 045007. http://stacks.iop.org/1758-5090/5/045007
Ostrowski, TD, EM Hasser, CM Heesch, DD Kline. H2O2 induces delayed hyperexcitability in nucleus tractus solitarii neurons. Neuroscience, accepted 2013. http://dx.doi.org/10.1016/j.neuroscience.2013.12.055
Johnson MS, Demarco VG, Heesch CM, Whaley-Connell AT, Schneider RI, Rehmer NT, Tilmon RD, Ferrario CM, Sowers JR.,Sex differences in baroreflex sensitivity, heart rate variability, and end organ damage in the TGR(mRen2)27 rat., Am J Physiol Heart Circ Physiol. 2011 Aug 5. [Epub ahead of print]PMID: 21821781
Heesch CM., Neurosteroid modulation of arterial baroreflex function in the rostral ventrolateral medulla., Auton Neurosci. 2011 Apr 26;161(1-2):28-33. Epub 2010 Nov 10., PMID: 21071286
Kline DD, King TL, Austgen JR, Heesch CM, Hasser EM., Sensory afferent and hypoxia-mediated activation of nucleus tractus solitarius neurons that project to the rostral ventrolateral medulla., Neuroscience. 2010 May 5;167(2):510-27. Epub 2010 Feb 12., PMID: 20153814
Kvochina L, Hasser EM, Heesch CM., Pregnancy decreases GABAergic inhibition of the hypothalamic paraventricular nucleus., Physiol Behav. 2009 May 25;97(2):171-9. Epub 2009 Feb 28., PMID: 19254733
Heesch CM, Zheng H, Foley CM, Mueller PJ, Hasser EM, Patel KP., Nitric oxide synthase activity and expression are decreased in the paraventricular nucleus of pregnant rats., Brain Res. 2009 Jan 28;1251:140-50. Epub 2008 Nov 19., PMID: 19041855
Austgen JR, Fong AY, Foley CM, Mueller PJ, Kline DD, Heesch CM, Hasser EM., Expression of Group I metabotropic glutamate receptors on phenotypically different cells within the nucleus of the solitary tract in the rat., Neuroscience. 2009 Mar 17;159(2):701-16. Epub 2008 Oct 17., PMID: 19013221
