Tissue and plasma angiotensin converting enzyme and the response to ACE inhibitor drugs.

Abstract

1. There is a body of circumstantial and direct evidence supporting the existence and functional importance of a tissue based RAS at a variety of sites. 2. The relation between circulatory and tissue based systems is complex. The relative importance of the two in determining haemodynamic effects is unknown. 3. Despite the wide range of ACE inhibitors already available, it remains unclear whether there are genuine differences related to tissue specificity. 4. Pathological states such as chronic cardiac failure need to be explored with regard to the contribution of tissue based ACE activities in generating acute and chronic haemodynamic responses to ACE inhibitors. 5. The role of tissue vs plasma ACE activity may be clarified by study of the relation between drug concentration and haemodynamic effect, provided that the temporal dissociation is examined and linked to circulating and tissue based changes in ACE activity, angiotensin peptides and sympathetic hormones.

Haemodynamic and hormonal responses to oral enalapril in salt depleted normotensive man.

“…The role of RAS activation in the blood pressure response to ACEI has practical importance in relation to clinical concerns about the 'first dose hypotension' which occasionally is symptomatic and rarely is associated with hypoperfusion damage. The origin and significance of this acute blood pressure fall is unclear (MacFadyen et al, 1991b) but many factors may play a role. With this model of RAS activation it will be possible to undertake controlled studies to investigate the contributions of a particular drug, dosage and the level of activation of the RAS.…”

Responses to low dose intravenous perindoprilat infusion in salt deplete/salt replete normotensive volunteers.

“…The origin of the blood pressure fall is unclear [35]. Surprisingly given the widespread use of these drugs, studies investigating the determinants of individual response are not available.…”

Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers: Evidence for and against the combination in the treatment of hypertension and proteinuria

“…Secondary high levels of tissue ACE activity found in the lung, blood vessels, myocardium, and kidneys [12] has also been proposed to mediate more long-term tissue damage like glomerular hypertrophy and left ventricular remodeling [13,14]. This is essential since tissue ACE activity is not always sufficiently blocked by regular doses of an ACE inhibitor, so even though circulating levels of angiotensin II are reduced, incessant tissue damage is ongoing.…”