Nitric Oxide Pathway Modulation for Therapeutic Intervention and Exercise Enhancement
Symposium — Sunday, April 23, 2024 — 10:30 AM - 12:30 PM — , Room W192B
Physiologists in Industry Committee — Chair: John Mattson — Co-Chair:
Nitric oxide (NO) vasodilatory properties have been utilized as a medical intervention for more than 130 years through the use of nitroglycerine. However, it wasnt until the discovery that endothelium-derived relaxing factor was in fact NO in the late 20th century that laboratories sought to augment its properties for physiological benefit. NO is produced endogenously by the reduction of L-arginine to L-citrulline via three distinct nitric oxide synthase (NOS) isoforms: endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). Specifically, NO acts via soluble guanylate cyclase (sGC), which catalyzes the production of cyclic guanosine monophosphate (cGMP), to function as a messenger in vascular, inflammatory, cell proliferative, tissue fibrotic, and metabolic control. In addition, dietary inorganic nitrate (NO3) delivered, for example, via ingested beetroot juice can be reduced to nitrite (NO2) and, subsequently, NO and other reactive nitrogen intermediates and impact haemodynamic and muscle metabolic function. Conversely, NO signaling dysfunction is associated with several risk factors for cardiopulmonary diseases (i.e. cardiovascular disease, pulmonary hypertension). Alternatively, dietary NO3 ingestion via sodium NO3 salt reduces blood pressure, lowers submaximal exercise oxygen uptake (VO2) and has been demonstrated to enhance exercise tolerance. This symposium will explore recently discovered therapeutic compounds and nutritional supplementation as a way to enhance NO pathway signaling in health and disease. Specifically, Bayer scientists will present the discovery and development of first in-class novel sGC modulators and academic cardiovascular physiologists will explore key models and strategies for understanding NO function in the cardiovascular system and current evidence for how vascular, muscle and exercise performance may be enhanced.
Speakers
- Discovery and Development of Soluble Guanylate Cyclase Stimulators and Activators
Johannes-Peter Stasch — Global Drug Discovery, Bayer Healthcare
- Development of Nitric Oxide -Soluble Guanylate Cyclase cyclic guanosine monophosphate Modulators for Medical Therapy
Peter Sandner — Global Drug Discovery, Bayer Healthcare
Nitric oxide and Muscle microvascular oxygen
transport: Health and heart failure
David Poole — Anatomy & Physiology, Kansas State University
Effects
of nitrite supplementation in models of physiological dysfunction
Amy Sindler — Department of Health & Human Physiology, University of Iowa