Meredith Hay

Meredith Hay

Professor, Physiology
Professor, Evelyn F Mcknight Brain Institute
Professor, Psychology
Professor, Physiological Sciences - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(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

Xue, B., Beltz, T. G., Yu, Y., Guo, F., Gomez-Sanchez, C. E., Hay, M., & Johnson, A. K. (2011). Central interactions of aldosterone and angiotensin II in aldosterone- and angiotensin II-induced hypertension. American journal of physiology. Heart and circulatory physiology, 300(2), H555-64.

Many studies have implicated both angiotensin II (ANG II) and aldosterone (Aldo) in the pathogenesis of hypertension, the progression of renal injury, and cardiac remodeling after myocardial infarction. In several cases, ANG II and Aldo have been shown to have synergistic interactions in the periphery. In the present studies, we tested the hypothesis that ANG II and Aldo interact centrally in Aldo- and ANG II-induced hypertension in male rats. In rats with blood pressure (BP) and heart rate (HR) measured by DSI telemetry, intracerebroventricular (icv) infusions of the mineralocorticoid receptor (MR) antagonists spironolactone and RU28318 or the angiotensin type 1 receptor (AT1R) antagonist irbesartan significantly inhibited Aldo-induced hypertension. In ANG II-induced hypertension, icv infusion of RU28318 significantly reduced the increase in BP. Moreover, icv infusions of the reactive oxygen species (ROS) scavenger tempol or the NADPH oxidase inhibitor apocynin attenuated Aldo-induced hypertension. To confirm these effects of pharmacological antagonists, icv injections of either recombinant adeno-associated virus carrying siRNA silencers of AT1aR (AT1aR-siRNA) or MR (MR-siRNA) significantly attenuated the development of Aldo-induced hypertension. The immunohistochemical and Western blot analyses of AT1aR-siRNA- or MR-siRNA-injected rats showed a marked reduction in the expression of AT1R or MR in the paraventricular nucleus compared with scrambled siRNA rats. When animals from all studies underwent ganglionic blockade with hexamethonium, there was a smaller reduction in the fall of BP in animals receiving icv AT1R or MR antagonists. These results suggest that ANG II and Aldo interact in the brain in a mutually cooperative manner such that the functional integrity of both brain AT1R and MR are necessary for hypertension to be induced by either systemic ANG II or Aldo. The pressor effects produced by systemic ANG II or Aldo involve increased central ROS and sympathetic outflow.

Xue, B., Zhang, Z., Beltz, T. G., Guo, F., Hay, M., & Johnson, A. K. (2014). Genetic knockdown of estrogen receptor alpha (ERα) in the subfornical organ augments angiotensin II-induced hypertension in female mice. American journal of physiology. Regulatory, integrative and comparative physiology, ajpregu.00406.2014.

The present study tested the hypotheses that 1) ERα in the brain plays a key role in the estrogen protective effects against angiotensin (ANG) II-induced hypertension, and 2) that the subfornical organ (SFO) is a key site where ERα mediates these protective actions. In this study, a "floxed" ERα transgenic mouse line (ERα(flox)) was used to create models in which ERα was knocked down in the brain or just in the SFO. Female mice with ERα ablated in the nervous system (Nestin-ERα(-) mice) showed greater increases in blood pressure (BP) in response to ANG II. Furthermore, females with ERα knockdown specifically in the SFO [SFO adenovirus-Cre (Ad-Cre) injected ERα(flox) mice] also showed an enhanced pressor response to ANG II. Immunohistochemical, RT-PCR and Western blot analyses revealed a marked reduction in the expression of ERα in nervous tissues and, in particular, in the SFO. These changes were not present in peripheral tissues in Nestin-ERα(-) mice or Ad-Cre injected ERα(flox) mice. mRNA expression of components of the renin-angiotensin system in the laminal terminalis were up-regulated in Nestin-ERα(-) mice. Moreover, ganglionic blockade on day 7 after ANG II infusions resulted in a greater reduction of BP in Nestin-ERα(-) mice or SFO Ad-Cre injected mice suggesting that knockdown of ERα in the nervous system or the SFO alone augments central ANG II-induced increase in sympathetic tone. The results indicate that interfering with the action of estrogen on SFO ERα is sufficient to abolish the protective effects of estrogen against ANG II-induced hypertension.

Xue, B., Pamidimukkala, J., Lubahn, D. B., & Hay, M. (2007). Estrogen receptor-alpha mediates estrogen protection from angiotensin II-induced hypertension in conscious female mice. American journal of physiology. Heart and circulatory physiology, 292(4), H1770-6.

It has been shown that the female sex hormones have a protective role in the development of angiotensin II (ANG II)-induced hypertension. The present study tested the hypotheses that 1) the estrogen receptor-alpha (ERalpha) is involved in the protective effects of estrogen against ANG II-induced hypertension and 2) central ERs are involved. Blood pressure (BP) was measured in female mice with the use of telemetry implants. ANG II (800 ng.kg(-1).min(-1)) was administered subcutaneously via an osmotic pump. Baseline BP in the intact, ovariectomized (OVX) wild-type (WT) and ERalpha knockout (ERalphaKO) mice was similar; however, the increase in BP induced by ANG II was greater in OVX WT (23.0 +/- 1.0 mmHg) and ERalphaKO mice (23.8 +/- 2.5 mmHg) than in intact WT mice (10.1 +/- 4.5 mmHg). In OVX WT mice, central infusion of 17beta-estradiol (E(2); 30 microg.kg(-1).day(-1)) attenuated the pressor effect of ANG II (7.0 +/- 0.4 mmHg), and this protective effect of E(2) was prevented by coadministration of ICI-182,780 (ICI; 1.5 microg.kg(-1).day(-1), 18.8 +/- 1.5 mmHg), a nonselective ER antagonist. Furthermore, central, but not peripheral, infusions of ICI augmented the pressor effects of ANG II in intact WT mice (17.8 +/- 4.2 mmHg). In contrast, the pressor effect of ANG II was unchanged in either central E(2)-treated OVX ERalphaKO mice (19.0 +/- 1.1 mmHg) or central ICI-treated intact ERalphaKO mice (19.6 +/- 1.6 mmHg). Lastly, ganglionic blockade on day 7 after ANG II infusions resulted in a greater reduction in BP in OVX WT, central ER antagonist-treated intact WT, central E(2) + ICI-treated OVX WT, ERalphaKO, and central E(2)- or ICI-treated ERalphaKO mice compared with that in intact WT mice given just ANG II. Together, these data indicate that ERalpha, especially central expression of the ER, mediates the protective effects of estrogen against ANG II-induced hypertension.

Yu, R., Hay, M., & Ticku, M. K. (1996). Chronic neurosteroid treatment attenuates single cell GABAA response and its potentiation by modulators in cortical neurons. Brain research, 706(1), 160-2.

In previous studies we have observed that chronic neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one (5 alpha 3 alpha) treatment produced downregulation of the GABAA receptors, heterologous uncoupling, and decreased heterologous efficacy at the GABAA receptor complex in cultured mammalian cortical neurons. In this study, using whole cell recording, we examined the consequence of chronic 5 alpha 3 alpha (1 microM; 5 days) treatment on GABA-induced currents in isolated cortical neurons. We observed that the GABA current was decreased by 78% after 5 days treatment of cortical cells with 1 microM 5 alpha 3 alpha. We also observed decreased pentobarbital, and 5 alpha 3 alpha potentiation of GABA currents after chronic 5 alpha 3 alpha treatment. These findings support the notion that GABA response, and its potentiation by pentobarbital, and neurosteroid, 5 alpha 3 alpha, are attenuated after chronic 5 alpha 3 alpha treatment.

Hay, M. (2015). The Good and the Bad: Immune Cells and Hypertension. Clin Sci (Lond)., 117(10), 830-1.