Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, an important
step in the control of blood pressure. The gene encoding for ACE is subject to an
insertion/deletion (I/D) polymorphism which is associated with different levels of the enzyme
in serum. This polymorphism accounts for 47% of the variability in serum ACE
concentrations between subjects but its relevance to tissue ACE is unknown. ACE inhibition
increases kinin level, for example bradykinin. Kinins have been proposed be involved in the
pathogenesis of cough due to ACE inhibitors, a common adverse effect in those prescribed
these drugs. A genetic link was proposed to explain the differing susceptibility of subjects to
develop cough. Those susceptible may differ in the cough reflexes initially or perhaps have
different degrees of tissue ACE activity. In this thesis I examined healthy subjects using
substrates and inhibitors of ACE to identify any possible differences in tissue ACE between
those of different ACE genotype. I also examined the natural history of ACE inhibitor cough
in particular changes in cough reflex and the possible roles of kinins in its aetiology. The
frequency of ACE genotype amongst those who developed cough was also examined
