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Figure 2.1: Diagram of blood vessels in cross section showing the endothelial layer
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Taken from 'Access Excellence'- The Heart and the Circulatory System by Roger E phillips Jr., from
the National Health Museum, "The Site for Health, Teachers and-Learners', t-+tl K st, Suite 1300,
Washington DC 2000s.
These and other researchers continued pursuing the identity of this substance with the
evolving characteristics becoming increasingly similar to a compound of nitrogen, resulting in
experiments comparing 'EDRF' with nitrogen oxides. Furchgott initially announced that
EDRF could actually be the inorganic gas 'NO' at a conference in July 1986 (Khan and
Furchgott 1987)' This same conclusion was proposed at the same conference by Ignarro as a
result of his experiments on bovine pulmonary arteries (Ignarro, Buga et al. l9g7; Ignarro,
Byrns et al. 1988). Similarly in 1987, Palmer, Fenige and Moncada showed that vascular
endothelial cells generated NO and that the amounts generated accounted for the biological
activity of the named EDRF mediator (Moncada, Palmer et al. 1988). This was a novel
suggestion as - until this time -
mediators.
gases had not been thought capable of acting as biological
It had been recognised that endothelium dependant relaxation of blood vessels was associated
with increased cyclic guanosine 3', 5' -monophosphate (cGMp) levels in vascular muscle.
This was demonstrated earlier in a number of studies using rat aorta (Rapoport and Murad
1983), rabbit aorta (Diamond and Chu 1983, Furchgott, 1983 #415), bovine coronary arteries
(Holzmann 1982) or bovine pulmonary arteries (Ignarro, Burke et al. 1984). Rises in cGMp
are produced by activation of soluble guanylate cyclase (sGC), a magnesium sensitive
hexodimer protein which contains two heme molecules. Under basal conditions, the guanylate
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