- Hormonal Regulation and Hypertension
- Renin-Angiotensin System Studies
- Receptor Mechanisms and Signaling
- Estrogen and related hormone effects
- Sodium Intake and Health
- Sex and Gender in Healthcare
- Blood Pressure and Hypertension Studies
- Menopause: Health Impacts and Treatments
- Birth, Development, and Health
- RNA Research and Splicing
- Nitric Oxide and Endothelin Effects
- RNA and protein synthesis mechanisms
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Neuroendocrine regulation and behavior
- Electrolyte and hormonal disorders
- Cholinesterase and Neurodegenerative Diseases
- Ion channel regulation and function
- Stress Responses and Cortisol
- Reproductive Biology and Fertility
- Endometriosis Research and Treatment
- Heart Rate Variability and Autonomic Control
- Ion Transport and Channel Regulation
- Neuropeptides and Animal Physiology
- Diversity and Career in Medicine
- Adipose Tissue and Metabolism
Georgetown University
2015-2024
Southern California University for Professional Studies
2024
University of Southern California
2022-2024
University of California, Davis
2024
Georgetown University Medical Center
2008-2023
Individual Differences
2010-2022
University of Arizona
2014-2022
Georgetown-Howard Universities Center for Clinical and Translational Science
2014-2022
Johns Hopkins University
1984-2022
Johns Hopkins Medicine
1984-2022
Men have higher blood pressure than women through much of life regardless race and ethnicity. This is a robust highly conserved sex difference that it also observed across species including dogs, rats, mice chickens found in induced, genetic transgenic animal models hypertension. Not only do the differences between ovarian testicular hormonal milieu contribute to this sexual dimorphism pressure, chromosomes play role themselves. review primarily focuses on epidemiological studies men...
The current novel coronavirus disease 2019 (COVID-19) pandemic is revealing profound differences between men and women in outcomes worldwide. In the United States, there has been inconsistent reporting analyses of male–female COVID-19 cases, hospitalizations, deaths. We seek to raise awareness about male-biased severe from COVID-19, highlighting mechanistic including expression activity angiotensin-converting enzyme 2 (ACE2) as well antiviral immunity. also highlight how sex comorbidities,...
Abstract Angiotensin II (AII) is a major regulator of cardiovascular function and fluid homeostasis. Recently, the cDNA for an AII receptor (AT1) was cloned from rat smooth muscle bovine adrenal. To search subtypes, we amplified adrenal cortex by PCR using primers based on AT1 receptor. The product distinct as indicated restriction enzyme analysis DNA sequencing. A full-length clone (2.2 kilobase pairs) encoding novel (AT3) obtained screening library. AT3 encodes Mr 40,959 protein with 95%...
Angotensin converting enzyme 2 (ACE2) is a newly discovered monocarboxypeptidase that counteracts the vasoconstrictor effects of angiotensin II (Ang II) by Ang to Ang-(1-7) in kidney and other tissues.ACE2 activity from renal homogenates was investigated using fluorogenic peptide substrate Mca-YVADAPK(Dnp)-OH, where Mca (7-methoxycoumarin-4-yl)-acetyl Dnp 2,4-dinitrophenyl.We found ACE2 expressed relative fluorescence units (RFU) MF1 mouse higher male (M) compared female (F) [ACE2...
ABSTRACT. This study examined the effects of estrogen deficiency by ovariectomy (OVX) and 17β-estradiol (E<sub>2</sub>) replacement (OVX+E<sub>2</sub>) on glomerulosclerosis tubulointerstitial fibrosis mechanisms contributing to these changes, including expression collagen type IV laminin, transforming growth factor-β (TGF-β), activity matrix metalloproteinases (MMP) in kidneys young (4 mo [4M]) aged (12 [12M]) Dahl salt-sensitive (DSS) rats maintained a low-salt (0.1% NaCl) diet. While...
The ovariectomized (OVX) Dahl salt-sensitive (DS) rat fed a low-salt diet is model of postmenopausal hypertension. In addition to estrogen loss, aging can also contribute We hypothesized that: (1) female DS rats on become hypertensive with age; (2) ovariectomy accelerates age-dependent hypertension in the caused by depletion; and (3) this correlates increased type 1 angiotensin receptor (AT R) number (Bmax). Blood pressure was monitored telemetry from 3 12 months AT R Bmax determined...
Sex differences in mean arterial pressure (MAP) are reported many experimental models of hypertension and ascribed to gonadal sex based on studies showing that gonadectomy hormone replacement affect MAP. The interpretation these studies, however, has been confounded by the chromosome complement (XX versus XY). To investigate independent sex, we used 4 core genotype mouse model which is separated from enabling comparisons among XX XY females males. We found that, gonadectomized (GDX)...
There is extensive evidence that activation of the immune system both necessary and required for development angiotensin II (Ang II)-induced hypertension in males. The purpose this study was to determine whether sex differences exist ability adaptive induce Ang II-dependent central renal T-cell infiltration during II-induced dependent. Recombinant activating gene-1 (Rag-1)(-/-) mice, lacking T B cells, were used. Male female Rag-1(-/-) mice received adoptive transfer male CD3(+) cells 3...
Studies suggest T cells modulate arterial pressure. Because robust sex differences exist in the immune system and hypertension, we investigated T-cell modulation of angiotensin II–induced increases mean pressure male (M) female (F) wild-type recombination-activating-gene-1–deficient (Rag1 −/− ) mice. Sex peak were lost Rag1 mice (mm Hg: wild-type-F, 136±4.9 versus wild-type-M, 153±1.7; P <0.02; -F, 135±2.1 -M, 141±3.8). Peak was 13 mm Hg higher after adoptive transfer (CD3 M →Rag1 -M) F...
The biphenylimidazole derivative losartan exemplifies a novel class of nonpeptide antagonists that selectively inhibit angiotensin I1 binding to the mammalian AT, receptor and have potentially wide application as anti-hypertensive agents.In contrast receptors, which high affinity for both peptide losartan, amphibian avian 11 receptors are pharmacologically distinct recognize but not antagonists.Mutant rat in non-conserved amino acids were replaced by corresponding residues constructed...
17beta-Oestradiol (E2)-mediated inhibition of angiotensin-converting enzyme (ACE) protects the E2-replete kidney from progression hypertensive renal disease. Angiotensin-converting 2 (ACE2), a homologue ACE, counters actions ACE by catalysing conversion angiotensin II (Ang II) to angiotensin(1-7) [Ang(1-7)]. We investigated E2 regulation ACE2 in wrap (RW) model hypertension rats. After 6 weeks on high-sodium diet (4% NaCl), activity was reduced cortex 31%, which mirrored similar decreases...
The U.S. National Institutes of Health (NIH) announced last May that steps will be taken to address the over-reliance on male cells and animals in preclinical research. To further this announcement, September 2014, scientists with varying perspectives came together at Georgetown University discuss following questions. (1) What metrics should NIH use assess tangible progress policy changes designed research? (2) How effective can education reducing research what educational initiatives...
Although the mechanisms are not understood, evidence suggests that 17beta-estradiol (E2) confers protection from cardiovascular and renal complications in many diseases. We have reported E2 decreases angiotensin type 1 receptors (AT1Rs) different tissues hypothesize exerts tonic inhibition on AT1Rs, reducing effects of ANG II. This study determined dihydrotestosterone (DHT) cortical estrogen (ERs) glomerular AT1R binding rats. Animals underwent sham operation, ovariectomy (Ovx) or...
Low rates of angiotensin II (Ang II) infusion raise blood pressure, renal vascular resistance (RVR), NADPH oxidase activity, and superoxide. We tested the hypothesis that these effects are ameliorated by extracellular superoxide dismutase (EC-SOD). EC-SOD knockout (-/-) wild type (+/+) mice were equipped with pressure telemeters infused subcutaneously Ang (400 ng/kg per minute) or vehicle for 2 weeks. During infusion, -/- had significantly (P<0.05) higher MAP (+/+: 107+/-3 mm Hg versus -/-:...
Abstract: Ethylcholine mustard aziridinium ion (AF64A, MEChMAz) has been proposed as a cholinergic neuronspecific neurotoxin. We report that in further studies on its mechanism of action incubation the neuroblastoma × glioma cell line, NG‐108‐15, with 100 μ M AF64A resulted rapid decrease cellular choline acetyltransferase (ChAT) activity which preceded cytotoxicity. Thus, 60–85% ChAT was measured within 5 h exposure, whereas lysis (measured release cytosolic enzyme lactate dehydrogenase...
The renal vasopressin V 2 receptor (V R) plays a critical role in physiological and pathophysiological processes associated with arginine (AVP)-induced antidiuresis. Because clinical data suggests that females may be more prone to hyponatremia from AVP-mediated antidiuresis, we investigated whether there are sex differences the expression function of R. In normal Sprague-Dawley rat kidneys, R mRNA protein was 2.6- 1.7-fold higher, respectively, compared males. To investigate potential...