Nitric oxide and asthma.

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.2-9 It has at least four roles in the lungs.3 These 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 NO endothelial, 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 ofNO in seconds.10 iNOs is part of the immune system and is induced by cytokines, endotoxin, and lipopolysaccharide resulting in formation of larger amounts of NO.11 However, this reaction involves gene transcription, and is therefore much slower, resulting in increased production ofNO over several hours or even days. It can be blocked by glucocorticosteroids. 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'monophosUniversity of phate (cGMP).12 13 The rise in cGMP results Deparment of Child in relaxation of smooth muscle but the mechHealth, 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 cna n S016 6YD Inactivation of enzymes containing transition