Nitric Oxide

Biology and Pathobiology

Louis J. Ignarro, Bruce Freeman, Louis J. Ignarro, Bruce Freeman

• Publisher: Academic Press
• Year: 2017
• ISBN:
  9780128043196
• Edition: 3
• Topic: Biological Sciences
• Subtopic: Biochemistry
• Index: Biological Sciences

Nitric Oxide: Biology and Pathobiology, Third Edition, provides information on nitric oxide, a signaling molecule of key importance for the cardiovascular system that regulates blood pressure and blood flow to different organs.

With recent links to the role of nitric oxide in the expression of healthy benefits of controlled diet and aerobic exercise, and the reactions of nitric oxide that can impact cell signaling, this book provides a comprehensive resource during a time when increased research attention is being paid across the fields of pharmacology, biochemistry, cell and molecular biology, chemistry, immunology, neurobiology, immunology, nutrition sciences, drug development and the clinical management of both acute and chronic diseases.

• Includes perspectives from Jack Lancaster on the discovery of EDRF and nitric oxide
• Provides detailed coverage of the new gaseous signaling agents
• Features expanded coverage on the principles of biology, including nitric oxide synthases, nitrite and nitrate biology and pathobiology, and signaling mechanisms
• Incorporates expanded pathobiology coverage, including nitric oxide and cardiovascular function, obesity, diabetes, and erectile function/dysfunction

Chapter 1

A Concise History of the Discovery of Mammalian Nitric Oxide (Nitrogen Monoxide) Biogenesis

Jack R. Lancaster, Jr. University of Pittsburgh School of Medicine, Pittsburgh, PA, United States

Abstract

In 1986–88 one of the most unexpected and important scientific paradigm shifts of the 20th century occurred, involving several seemingly unrelated phenomena in cardiovascular, immunological, and neurochemical research. It was discovered that mammalian cells produce the molecule nitric oxide (chemical formula ·NO), which had previously been known in animals as primarily a poison and pollutant. First discovered as a critical signal that is produced by and regulates multiple functions of the vasculature (for which the 1998 Nobel Prize in Physiology or Medicine was awarded to Robert Furchgott, Louis Ignarro, and Ferid Murad), researchers in immunology and neuroscience immediately recognized that many previously puzzling phenomena are explained by ·NO. Here I present the historical development of this remarkable discovery and the initial establishment of the chemical and physical principles that define its extraordinarily pleiotropic biological actions, emphasizing the importance of the concept.

Keywords

nitric oxide

nitric acid

hemoglobin

metals

nitrovasodilator

immune system

neurotransmitter

Introduction

Twenty years ago, on the day after Christmas 1986, Louis Ignarro submitted the first manuscript to claim that eukaryotic cells produce the unique molecule nitric oxide (·NO) [1]. Its role as a major regulator of vascular tone was the subject of this report, but it soon became clear that researchers in two other fields (immunology and neurotransmission) were studying phenomena that are the result of the same molecule. This convergence of three seemingly unrelated fields initiated an explosion of discoveries in the remarkable importance of ·NO in virtually every physiological and pathophysiological process. Here I provide a concise chronology of these discoveries.

·NO and NO_x Prior to 1986

Ancient Human/NO_x, ·NO Relationships

The relationship between humans and nitrogen oxides (NO_x) is a truly ancient one, dating from around 3000 years ago. Undoubtedly the first use of NO_x was as a food preservative, dating to the use of cave “wall saltpetre” [Ca(NO₃)₂] for meat curing in China and India [2]. Salt curing was practiced extensively by the early Phoenicians, Romans, and Greeks. In addition to curing, the beneficial cardiovascular effects of NO_x were also recognized. In 1901 the British explorer Sir Aurel Stein discovered a remarkable collection of manuscripts at a Buddhist shrine i...