Key result
Oral administration of five ACE inhibitors in Spontaneously Hypertensive Rats produced significant inhibition of brain and vascular ACE activity at doses corresponding to peak blood pressure reduction.
Why the study?
Does oral administration of ACE inhibitors reduce tissue ACE activity in correlation with blood pressure reduction in Spontaneously Hypertensive Rats?
Does oral administration of ACE inhibitors reduce tissue ACE activity in correlation with blood pressure reduction in Spontaneously Hypertensive Rats?
Maximal antihypertensive effects of ACE inhibitors may be mediated by inhibition of ACE in vascular tissues and the brain.
Supports tissue ACE inhibition in BP lowering in rats; leaves open human translation and clinical relevance.
A series of five structurally distinct ACE inhibitors were evaluated for their ability to inhibit tissue ACE activity in the SHR after oral administration. In the first series of experiments, the ACE inhibitors captopril, enalapril, pentopril, CGS 14824A and CGS 16617 were given to groups of SHR at doses that produced a 15 to 20 mm Hg reduction in blood pressure within 1 hour. Under these conditions of dose and time, only captopril significantly inhibited brain ACE activity (43%), whereas inhibition of serum ACE activity ranged from 72% to 99% with these agents. Inhibition of aortic ACE activity ranged from 54% to 87%, and lung ACE inhibition varied from 50% to 83%. In the second series of experiments, SHR were administered higher doses of each ACE inhibitor such that these compounds produced peak reductions in blood pressure (-25 mm Hg to -33 mm Hg) within a range of 2 to 6 hours. When tissue ACE activity was measured at the time corresponding to peak reduction in blood pressure, all five ACE inhibitors produced a significant inhibition of brain ACE activity ranging from 21% to 76%. Serum ACE activity was almost completely inhibited by these agents, with the exception of captopril (62% inhibition). The inhibition of aortic ACE activity ranged from 79% to 99%, while the inhibition of lung ACE activity did not increase under these conditions. These data suggest that ACE inhibitors may exert their maximal antihypertensive effects by inhibiting ACE in vascular tissues and brain.
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Norman et al. (1987) studied Hypertension. ACE inhibitors (captopril, enalapril, pentopril, CGS 14824A, CGS 16617) was evaluated on Tissue ACE activity inhibition (brain, serum, aortic, lung). Oral administration of five ACE inhibitors in Spontaneously Hypertensive Rats produced significant inhibition of brain and vascular ACE activity at doses corresponding to peak blood pressure reduction.