Nitric oxide and asthma.

Nitric oxide and asthmaBozhena Zoritch Since nitric oxide (NO) was first described as endothelium derived relaxing factor (EDRF),I there has been compelling evidence that NO is involved in very many biological processes.2-9It has at least four roles in the lungs.3These are as a pulmonary vasodilator, bronchodilator, non-adrenergic non-cholinergic transmitter, and inflammatory mediator.There are three types of NO synthase, the enzyme catalysing the formation of NOendothelial, neuronal (both known as constitutive or cNOs), and macrophage or inducible (iNOs) forms (fig 1).8 Agonists activate cNOs by an increase in calcium ion (Ca2+) concentration resulting in release of NO in seconds.10iNOs is part of the immune system and is induced by cytokines, endotoxin, and lipopolysaccharide resulting in formation of larger amounts of NO.11However, this reaction involves gene transcription, and is therefore much slower, resulting in increased production of NO over several hours or even days.It can be blocked by glucocorti- costeroids.Once formed, NO activates soluble guanylyl cyclase (sGG) after binding to its haem moiety to initiate a three dimensional change in the shape of the enzyme which increases its activity and consequently the production of cyclic guanosine 3'5'monophos-University of phate (cGMP).1213 The rise in cGMP results Deparment of Child in relaxation of smooth muscle but the mech- Health, Southampton anism by which this happens is unknown.General Hospital, When produced in large quantities, NO is Tremona Road, involved in tissue damage and cell death.Southampton