Endocrine System Commons^™

Central Activation Of Orl-1 Receptors In Heart Failure Models, Jeffrey Angell

Theses & Dissertations

Heart failure is a prevalent and debilitating disease associated with high morbidity and mortality rates worldwide and is the leading cause of death in the United States. While various therapeutic strategies have been developed and approved to manage heart failure, exploration of novel targets and mechanisms are essential for improving patient outcomes. This thesis investigates the therapeutic potential of the central activation of opioid receptor-like 1 (ORL-1) by nociceptin in a rodent heart failure model.

Furthermore, this study aims to elucidate the central mechanisms underlying nociceptin induced cardiovascular and renal effects in heart failure. This involves investigating neuronal pathways and …

Severe Mixed Mitral Valve Disease Due To Massive Mitral Annular Calcification: A Case Report And Literature Review, Fateh Ali Tipoo Sultan, Sheema Saadia

Section of Cardiology

We present an unusual case of massive mitral annular calcification (MAC) leading to severe mixed mitral valve disease, viz severe mitral regurgitation and severe mitral stenosis. To our knowledge, severe mixed mitral valve disease secondary to MAC is extremely rare. The patient (a 65-year-old lady) presented with worsening shortness of breath and signs of congestive heart failure. Echocardiographic examination revealed massive mitral annular calcification. Despite the massive annular calcification, she had experienced neither embolism nor endocarditis in the past. Because of severe symptomatic mitral regurgitation and mitral stenosis, surgery was advised; however, the patient declined it.

Capillary Endothelia From Two Adpkd Patients Are Polyploidy, Sarmed H. Kathem, Wissam A. Aboualaiwi, Xiaolin Zi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Bilateral renal cyst formation is the main feature of autosomal dominant polycystic kidney disease (ADPKD). We and other laboratories have previously shown that cystlining epithelia of kidneys from ADPKD patients are characterized by polyploidy. In this report, we show that endothelia from the renal capillary beds of two ADPKD patients are also polyploidy. Spectral karyotyping study further confirms our flow cytometry analyses. We suggest that polyploidy may be used as a potential cellular marker in ADPKD.

Dopaminergic Signaling Within The Primary Cilia In The Renovascular System, Kimberly F. Atkinson, Samred H. Kathem, Xingjian Jin, Brian S. Muntean, Wissam A. Aboualaiwi, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Activation of dopamine receptor type-5 (DR5) has been known to reduce systemic blood pressure, most likely by increasing renal vasodilation and enhancing natriuresis in the kidney. However, the mechanism of DR5 in natriuresis and vasodilation was not clearly known. We have previously shown that DR5 is localized to primary cilia of proximal renal epithelial and vascular endothelial cells. We here show that selective activation of DR5 specifically induces calcium influx only in the primary cilia, whereas non-selective activation of dopamine receptor induces calcium fluxes in both cilioplasm and cytoplasm. Cilia-independent signaling induced by thrombin only shows calcium signaling within cytoplasm. …

Primary Cilia Regulates The Directional Migration And Barrier Integrity Of Endothelial Cells Through The Modulation Of Hsp27 Dependent Actin Cytoskeletal Organization, Thomas J. Jones, Ravi K. Adapala, Werner J. Geldenhuys, Chris Bursley, Wissam A. Aboualaiwi, Surya M. Nauli, Charles K. Thodeti

Pharmacy Faculty Articles and Research

Cilia are mechanosensing organelles that communicate extracellular signals into intracellular responses. Altered functions of primary cilia play a key role in the development of various diseases including polycystic kidney disease. Here, we show that endothelial cells from the oak ridge polycystic kidney (Tg737orpk/orpk) mouse, with impaired cilia assembly, exhibit a reduction in the actin stress fibers and focal adhesions compared to wild type. In contrast, endothelial cells from polycystin-1 deficient mice (pkd1null/null), with impaired cilia function, display robust stress fibers and focal adhesion assembly. We found that the Tg737orpk/orpk cells exhibit impaired directional migration and endothelial cell monolayer permeability compared …

The Mechanosensory Role Of Primary Cilia In Vascular Hypertension, Surya M. Nauli, Xingjian Jin, Beerend P. Hierck

Pharmacy Faculty Articles and Research

Local regulation of vascular tone plays an important role in cardiovascular control of blood pressure. Aside from chemical or hormonal regulations, this local homeostasis is highly regulated by fluid-shear stress. It was previously unclear how vascular endothelial cells were able to sense fluid-shear stress. The cellular functions of mechanosensory cilia within vascular system have emerged recently. In particular, hypertension is insidious and remains a continuous problem that evolves during the course of polycystic kidney disease (PKD). The basic and clinical perspectives on primary cilia are discussed with regard to the pathogenesis of hypertension in PKD.

Hypertension In Autosomal Dominant Polycystic Kidney Disease: A Clinical And Basic Science Perspective, Shobha Ratnam, Surya M. Nauli

Pharmacy Faculty Articles and Research

Cardiovascular complications are major causes of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). In particular, hypertension is insidious and remains a continuous problem that evolves during the course of the disease. Hypertension in ADPKD has been associated with abnormality in the renin-angiotensin-aldosterone system (RAAS). Early vascular changes have also been reported in young ADPKD patients. In addition, the cellular functions of mechanosensory cilia within vascular system have emerged recently. The basic and clinical perspectives of RAAS, vascular remodeling and sensory cilia are reviewed with regard to hypertension in ADPKD

Fetal Whole-Body Fluid, Cardiovascular And Endocrine Dynamics : Computer Analysis Of Regulatory Mechanisms, Peter Stuart Gold

Loma Linda University Electronic Theses, Dissertations & Projects

The dynamics of transcapillary fluid and protein distribution and endocrine regulation of cardiovascular function were studied in chronically instrumented fetal sheep during the third trimester. Average experimental changes in vascular pressures, blood volume, plasma hormone concentrations, hematocrit and plasma protein concentration were analyzed using mathematical modeling and parameter optimization techniques in order to determine values for the major parameters which regulate fluid, protein and endocrine dynamics and to determine endocrine dose-response relationships to changes in cardiovascular function. The hormones which were considered are arginine vasopressin (AVP), angiotensin II (AII), epinephrine (EPI) and norepinephrine (NE). Vascular disturbances which were considered include …