Meredith Hay
Professor, BIO5 Institute
Professor, Evelyn F Mcknight Brain Institute
Professor, Physiology
Professor, Psychology
Professor, Physiological Sciences - GIDP
Primary Department
Department Affiliations
(520) 626-7384
Work Summary
Our lab is focused on the development of novel peptides to inhibit this inflammatory cascade and improve brain blood flow. These peptides are designed to significantly improve serum half-life and penetrate the blood-brain-barrier. These peptides act to inhibit the inflammatory pathways at both the level of brain blood vessels and the brain itself.
Research Interest
Dr. Hay is internationally known for her work in cardiovascular neurobiology and her current studies on the role of sex and sex hormones in the development of hypertension. She has been continuously funded by the NIH and other sources for the past 26 years. She has extensive experience in central renin angiotensin mechanisms, neurophysiology and reactive oxygen and cytosolic calcium neuroimaging and in advancing knowledge related to central mechanisms of neurohumoral control of the circulation. She is a Professor of Physiology at the University of Arizona College of Medicine and maintains active participation in the American Physiological Society, the Society of Neuroscience, AAAS, and has served on numerous editorial boards of prestigious scientific journals and grant review panels for the National Institutes of Health and the National American Heart Association. The primary focus of Dr. Hay’s laboratory is the understanding of the biophysical and cellular mechanisms underlying neurotransmitter modulation of sympathetic outflow and ultimately arterial blood pressure. The scientific questions being asked are: 1) What central neurotransmitter mechanisms are involved in the normal regulation of cardiovascular function? 2) Does the development of some forms of hypertension involve biophysical or molecular alteration in the neurotransmitter mechanisms regulating cardiovascular control? 3) Can these central signal transduction systems, which control sympathetic outflow and ultimately arterial blood pressure, be altered in order to prevent or attenuate the development of some forms of hypertension? 4) Are there gender related differences in some of these mechanisms?Dr. Hay has extensive national experience in university-wide administration and interdisciplinary research program development. Prior to coming to the University of Arizona in 2008 as Executive Vice President and Provost, Dr. Hay was the Vice President for Research for the University of Iowa, where she worked with state and federal lawmakers, private sector representatives, and local community groups to broaden both private and public support for research universities. Dr. Hay, a Texas native, earned her B.A. in psychology from the University of Colorado, Denver, her M.S. in neurobiology from the University of Texas at San Antonio, and her Ph.D. in cardiovascular pharmacology from the University of Texas Health Sciences Center, San Antonio. She trained as a postdoctoral fellow in the Cardiovascular Center at the University of Iowa College of Medicine and in the Department of Molecular Physiology and Biophysics at Baylor College of Medicine in Houston. She was a tenured faculty member of the University of Missouri-Columbia from 1996-2005. Prior to Missouri, she was a faculty member in the Department of Physiology at the University of Texas Health Science Center- San Antonio.

Publications

Hay, M., Vanderah, T. W., Samareh-Jahani, F., Constantopoulos, E., Uprety, A. J., & Barnes, C. A. (2017). Cognitive impairment in heart failure: A protective role for Angiotensin-(1-7). Behavioral Neuroscience, 131, 99-114.
BIO5 Collaborators
Carol A Barnes, Meredith Hay
Pollow, D. P., Uhrlaub, J., Romero-Aleshire, M. J., Sandberg, K., Nikolich-Zugich, J., Brooks, H. L., & Hay, M. (2014). Sex differences in T-lymphocyte tissue infiltration and development of angiotensin II hypertension. Hypertension, 64(2), 384-90.
BIO5 Collaborators
Heddwen L Brooks, Meredith Hay

There is extensive evidence that activation of the immune system is both necessary and required for the development of angiotensin II (Ang II)-induced hypertension in males. The purpose of this study was to determine whether sex differences exist in the ability of the adaptive immune system to induce Ang II-dependent hypertension and whether central and renal T-cell infiltration during Ang II-induced hypertension is sex dependent. Recombinant activating gene-1 (Rag-1)(-/-) mice, lacking both T and B cells, were used. Male and female Rag-1(-/-) mice received adoptive transfer of male CD3(+) T cells 3 weeks before 14-day Ang II infusion (490 ng/kg per minute). Blood pressure was monitored via tail cuff. In the absence of T cells, systolic blood pressure responses to Ang II were similar between sexes (Δ22.1 mm Hg males versus Δ18 mm : Hg females). After adoptive transfer of male T cells, Ang II significantly increased systolic blood pressure in males (Δ37.7 mm : Hg; P

Hay, M., & Hasser, E. M. (1998). Measurement of synaptic vesicle exocytosis in aortic baroreceptor neurons. The American journal of physiology, 275(2 Pt 2), H710-6.

The purpose of this study was to evaluate the use of the fluorescent membrane label FM1-43 as a measure of synaptic terminal exocytosis during stimulation of labeled aortic baroreceptor and unlabeled nodose ganglia neurons. Activation of the nerve terminals with electrical stimulation or depolarization with 90 mM KCl in the presence of 2.0 microM FM1-43 resulted in bright, punctate staining of synaptic boutons. Additional depolarization in the absence of dye resulted in destaining with a time course that was consistent and repeatable in multiple boutons within a given terminal. Destaining was dependent on calcium influx and was blocked by bath application of 100 microM CdCl2. Whole cell patch-clamp studies have reported that depolarization-induced calcium influx in aortic baroreceptor cell bodies is predominantly caused by the activation of omega-conotoxin GVIA (omega-CgTx)-sensitive N-type calcium channels. In addition, these N-type channels have been shown to be inhibited by activation of metabotropic glutamate receptors. In the present study, exocytosis in aortic baroreceptor terminals was not affected by bath application of 5 microM nifedipine and only partially inhibited by bath application of 2.0 microM omega-CgTx. However, depolarization-induced exocytosis was significantly inhibited by bath application of 200 microM L-AP4, a type III metabotropic glutamate receptor agonist. Results from this study suggest that 1) FM1-43 can be used to measure synaptic vesicle exocytosis in baroreceptor neurons; 2) the N-type calcium channel may not be involved in the initial phase of vesicle exocytosis; and 3) activation of L-AP4-sensitive metabotropic glutamate receptors inhibits 90 mM KCl-induced vesicle release.

Hay, M., & Lindsley, K. A. (1999). AMPA receptor activation of area postrema neurons. The American journal of physiology, 276(2 Pt 2), R586-90.

This study reports on the effects of activation of ionotropic glutamate receptors on area postrema neuron cytosolic calcium concentration ([Ca2+]i). In 140 of 242 area postrema neurons isolated from postnatal rats, application of 100 microM L-glutamate (L-Glu) resulted in a significant increase in [Ca2+]i. The remaining neurons were unaffected. The effects of L-Glu on area postrema [Ca2+]i were dose dependent, with a threshold of response near 1.0 microM and maximal response near 100 microM. To determine if the response of L-Glu in area postrema neurons was due to activation of ionotropic glutamate receptors, the effects of the broad-spectrum ionotropic glutamate receptor antagonist kynurinic acid (Kyn) was determined. Application of 1.0 mM Kyn resulted in a 62.6 +/- 4% inhibition of the L-Glu-evoked response. Application of the selective N-methyl-D-aspartic acid (NMDA) antagonist 2-amino-5-phosphonopentanoic acid had no effect on the response of area postrema neurons to 100 microM L-Glu. In contrast, application of the selective DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA)/kainate receptor antagonist 6,7-dinitroquinoxaline (DNQX) effectively blocked the 100 microM L-Glu response. Application of (+/-)-AMPA mimicked the effects observed with L-Glu and was selectively blocked by DNQX. These results suggest that L-Glu activation of area postrema neurons involves activation of AMPA receptors but not NMDA receptors.

Hay, M., Xue, B., & Johnson, A. K. (2014). Yes! Sex matters: sex, the brain and blood pressure. Current hypertension reports, 16(8), 458.

The role of the brain in hypertension between the sexes is known to be important especially with regards to the effects of circulating sex hormones. A number of different brain regions important for regulation of sympathetic outflow and blood pressure express estrogen receptors (ERα and ERβ). Estradiol, acting predominantly via the ERα, inhibits angiotensin II activation of the area postrema and subfornical organ neurons and inhibits reactive oxygen generation that is required for the development of Angiotensin II-induced neurogenic hypertension. Estradiol activation of ERβ within the paraventricular nucleus and the rostral ventral lateral medulla inhibits these neurons and inhibits angiotensin II, or aldosterone induced increases in sympathetic outflow and hypertension. Understanding the cellular and molecular mechanisms underlying ERα and ERβ actions within key brain regions regulating blood pressure will be essential for the development of "next generation" selective estrogen receptor modulators (SERMS) that can be used clinically for the treatment of neurogenic hypertension.