PT  - JOURNAL ARTICLE
AU  - Olivier Costerousse
AU  - Jacqueline Allegrini
AU  - Jean-Paul Clozel
AU  - Joël Ménard
AU  - François Alhenc-Gelas
TI  - Angiotensin I-Converting Enzyme Inhibition but Not Angiotensin II Suppression Alters Angiotensin I-Converting Enzyme Gene Expression in Vessels and Epithelia
DP  - 1998 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1180--1187
VI  - 284
IP  - 3
4099  - http://jpet.aspetjournals.org/content/284/3/1180.short
4100  - http://jpet.aspetjournals.org/content/284/3/1180.full
SO  - J Pharmacol Exp Ther1998 Mar 01; 284
AB  - The concentration of angiotensin-converting enzyme (ACE) increases during chronic treatment with ACE inhibitors for unknown reasons. We investigated whether alterations in ACE mRNA and ACE concentration occur in the different tissues during ACE inhibition and the role of angiotensins in these regulations by comparing ACE inhibitors with other blockers of the renin-angiotensin system. Enalapril, an ACE inhibitor, in the range of 0.3 to 10 mg/kg/day in rats induced dose- and time-dependant increases in plasma ACE up to two to three times control values. There were significant increases in the steady state ACE mRNA in the lung (32%), duodenum (64%) and aorta (324%) and 40% to 140% increases in membrane-bound enzyme concentration in these tissues and in the heart and kidney. The ACE content of purified duodenal brush border was increased by 80%, but the enzyme and its mRNA in the testis were not altered. The angiotensin II receptor antagonist losartan at several regimens of up to 30 mg/kg twice a day for 14 days produced no change in plasma ACE level or lung ACE mRNA. The human renin inhibitor ciprokiren was tested in guinea pigs, a species sensitive to this compound. Both enalapril and cilazapril induced 2-fold increases in plasma ACE, but ciprokiren (24 mg/kg/day for 12 days) had no effect. Enalapril treatment of BN/Kat rats (lacking circulating kininogens) caused a similar increase in ACE as in other rats. This study documents a general increase in ACEgene expression and enzyme concentration in tissues during ACE inhibition, with the exception of the testis, most probably reflecting an activation of the 5′, so-called somatic promoter of theACE gene. Angiotensins are not involved in this regulation and do not seem to control ACE gene expression in normal rodents. The American Society for Pharmacology and Experimental Therapeutics