A5078793399- Nitric Oxide and Endothelin Effects
- Regulation of Appetite and Obesity
- Heart Rate Variability and Autonomic Control
- Biochemical Analysis and Sensing Techniques
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiovascular Health and Disease Prevention
- Blood Pressure and Hypertension Studies
- Dietary Effects on Health
- Pharmacology and Obesity Treatment
- Cerebrovascular and Carotid Artery Diseases
- Pulmonary Hypertension Research and Treatments
- Folate and B Vitamins Research
- Thermoregulation and physiological responses
- Cardiovascular and exercise physiology
- Renin-Angiotensin System Studies
- Hormonal Regulation and Hypertension
- Cardiovascular Disease and Adiposity
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Pregnancy and preeclampsia studies
- Migraine and Headache Studies
- Diet and metabolism studies
- Diabetes Treatment and Management
- Bipolar Disorder and Treatment
- Pancreatic function and diabetes
Johnston Memorial Hospital
2024-2025
Ballad Health
2025
University of Oxford
2021-2023
Novo Nordisk (United Kingdom)
2019-2023
Auburn University
2020
AstraZeneca (Sweden)
2017-2019
University of Iowa
2008-2017
Montgomery County Department of Health and Human Services
2014
University of Iowa Health Care
2013
University of Iowa Hospitals and Clinics
2000-2012
Leptin is a peptide hormone produced by adipose tissue which acts centrally to decrease appetite and increase energy expenditure. Although leptin increases norepinephrine turnover in thermogenic tissues, the effects of on directly measured sympathetic nerve activity other tissues are not known. We examined intravenous vehicle brown tissue, kidney, hindlimb, adrenal gland anesthetized Sprague-Dawley rats. Intravenous infusion mouse over 3 h (total dose 10-1,000 microg/kg) increased plasma...
Background —Patients with obstructive sleep apnea (OSA) experience repetitive episodic hypoxemia consequent sympathetic activation and marked blood pressure surges, each of which may impair endothelial function. We tested the hypothesis that patients OSA have impaired endothelium-dependent vasodilation, even in absence overt cardiovascular disease. Methods Results —We studied 8 (age 44±4 years) 9 obese control subjects 48±3 years). Patients were newly diagnosed, never treated for OSA, on no...
To evaluate blood pressure and humoral vasoconstrictor responses to recurrent episodes of obstructive sleep apnea the effects therapy by means continuous positive airway pressure.We prospectively evaluated overnight changes in hemodynamics, oxygen saturation, apnea-hypopnea index, circulating endothelin-1, norepinephrine plasma renin activity 22 patients with severe before after successful using (three measurements). Measurements endothelin-1 were also obtained on three occasions, at similar...
Background —Moderate elevations in plasma homocyst(e)ine concentrations are associated with atherosclerosis and hypertension. We tested the hypothesis that experimental perturbation of homocysteine levels produces resistance conduit vessel endothelial dysfunction this occurs through increased oxidant stress. Methods Results —Oral administration l -methionine (100 mg/kg) was used to induce moderate hyperhomocyst(e)inemia (≈25 μmol/L) healthy human subjects. Endothelial function forearm...
Human in vitro physiological models studying disease and drug treatment effects are urgently needed as more relevant tools to identify new targets therapies. We have developed a human microfluidic two-organ-chip model study pancreatic islet-liver cross-talk based on insulin glucose regulation. established robust co-culture of islet microtissues liver spheroids maintaining functional responses up 15 days an insulin-free medium. Functional coupling, demonstrated by released from the response...
Nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of advanced chronic disease. The progression NAFLD, including nonalcoholic steatohepatitis (NASH), has strong genetic component, and the most robust contributor patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 encoding 148M protein sequence variant. We hypothesized that suppressing expression PNPLA3 mutant would exert beneficial effect on entire spectrum NAFLD. examined effects liver-targeted...
Leptin plays an important role in regulation of body weight through food intake and sympathetically mediated thermogenesis. The hypothalamic melanocortin system, via activation the melanocortin-4 receptor (MC4-R), decreases appetite weight, but its effects on sympathetic nerve activity (SNA) are unknown. In addition, it is not known whether sympathoactivation to leptin by system. We tested interactions between these systems brown adipose tissue (BAT) renal lumbar SNA anesthetized...
Background Although local inhibition of the generation or actions endothelin-1 has been shown to cause forearm vasodilatation, systemic effects endothelin receptor blockade in healthy humans are unknown. We therefore investigated cardiovascular a potent peptide ET A/B antagonist, TAK-044, men. Methods and Results Two randomized, placebo-controlled, crossover studies were performed. In nine subjects, TAK-044 (10 1000 mg IV over 15-minute period) caused sustained dose-dependent peripheral...
Leptin is an adipocyte-derived hormone that plays a key role in the regulation of body weight through its actions on appetite and metabolism. also increases sympathetic nerve activity (SNA) blood pressure. We tested hypothesis diet-induced obesity associated with resistance to metabolic leptin but preservation renal SNA arterial pressure effects, leading hypertension. Mice were fed high-fat diet for 10 weeks induce moderate obesity. The decrease food intake induced by intraperitoneal or...
Objective: To examine whether endogenous production of the endotheliumderived vasodilator nitric oxide influences blood pressure in healthy humans Methods: After preliminary pilot dose-ranging studies, 3mg/kg NG-monomethyl-l-arginine (l-NMMA), an inhibitor synthase, and saline placebo were infused intravenously over 5 min to eight subjects a two-phase, randomized, single-blind crossover study. Blood cardiac renal function measured Results: Compared with placebo, L-NMMA increased mean...
The role of endothelin ETB receptors in mediating vasoconstriction humans is unclear. As yet, there have been no vivo studies resistance vessels, and vitro data contradictory. We therefore investigated the function human forearm hand capacitance vessels using endothelin-1 as a nonselective agonist at ETA endothelin-3 sarafotoxin S6c selective agonists receptor.A series single-blind were performed, each six healthy men. Brachial artery infusion caused slow-onset dose-dependent...
Abstract To determine whether leptin has insulin sensitizing effects in normal rodents, we measured plasma glucose and concentrations male Sprague-Dawley rats treated with or vehicle by continuous sc infusion for 48 h. In additional experiments, examined the acute effect of iv upon sensitivity under conditions clamped glycemia. Subcutaneous was administered at 10.0 1.0 μg/h. avoid confounding differences food intake, both leptin- vehicle-treated were fasted during 48-h period infusion....
Objective Recent advances in understanding the neuroendocrine pathways regulating appetite, metabolism and body weight afford an opportunity to explore further mechanisms by which obesity influences arterial pressure. ob/ob(Lepob/Lepob) mice have a mutation ob gene are leptin-deficient. Leptin possesses pressor actions has been shown increase pressure when infused chronically or over-expressed transgenically. In contrast, agouti yellow obese(Ay) over-expression of peptide that blocks...
Background— Cigarette smoking causes endothelial dysfunction, possibly through increased oxidant stress. The enzyme xanthine oxidase produces oxidative free radicals. We tested the hypothesis that contributes to dysfunction in cigarette smokers by administering inhibitor allopurinol. Methods and Results— Fourteen (31±4 pack years) 14 age- sex-matched healthy non-smoking control subjects participated a single-blinded, randomized, 2-phase crossover study. All had no other risk factors for...
Severe sepsis is a systemic inflammatory response to infection resulting in acute organ dysfunction. Vascular perfusion abnormalities are implicated the pathology of failure, but studies microvascular function human limited. We hypothesized that impaired responses reactive hyperemia lead oxygen delivery relative needs tissue and these impairments would be associated with failure sepsis. studied 24 severe subjects h after recognition dysfunction; 15 healthy served as controls. Near-infrared...
Leptin, a hormone secreted by adipose tissue, acts to inhibit appetite and promote metabolism, thereby reducing body weight. Leptin also increases sympathetic activity arterial pressure. Several murine models of obesity, including agouti obese mice, exhibit resistance the anorexic weight-reducing effects leptin. Hypertension in mice has been attributed hyperleptinemia. These observations pose seeming paradox. If these are leptin-resistant, then how can leptin contribute hypertension? We...
Hyperhomocyst(e)inaemia is associated with endothelial dysfunction in animals and humans. Mechanisms responsible for hyperhomocyst(e)inaemia are poorly understood, but may involve impaired bioavailability of endothelium-derived nitric oxide (NO). We hypothesized that acute elevation homocyst(e)ine by oral methionine loading stimulate the formation asymmetrical dimethylarginine (ADMA), an endogenous inhibitor NO synthase, due to a transmethylation reaction during from methionine. studied nine...