Role of the tissue renin-angiotensin system in the action of angiotensin-converting enzyme inhibitors.
The mechanism of the blood pressure-lowering action of chronic administration of angiotensin-converting enzyme (ACE) inhibitors is still controversial. We investigated the effects of the ACE inhibitors, captopril and perindopril, on the renin-angiotensin system (RAS) in plasma and tissues (adrenal gland and kidney) in the rat. Captopril or perindopril was infused intraperitoneally into rats via a mini-osmotic pump for 6 days at a rate of 0.5 or 0.25 mg/kg/hr, respectively. Perindopril markedly increased plasma renin concentration (PRC) from 12.7 +/- 1.1 to 867 +/- 59 ng Ang I/ml/hr and significantly inhibited plasma angiotensin II (Ang II) from 17.5 +/- 3.5 to 7.8 +/- 0.6 pg/ml and plasma ACE activity from 31.6 +/- 1.7 to 1.7 +/- 0.3 U/liter. Captopril also increased PRC from 12.1 +/- 2.1 to 147 +/- 17 ng Ang I/ml/hr. However, it did not inhibit plasma Ang II (20.6 +/- 1.9 vs 22.0 +/- 2.1 pg/ml, N.S.) and increased plasma ACE activity from 35.9 +/- 1.8 to 65.0 +/- 4.8 U/liter. Perindopril increased kidney renin from 625.3 +/- 84.6 to 2152.3 +/- 233.4 micrograms/g/hr, while captopril produced a modest but insignificant rise in kidney renin (708.0 +/- 107.1 vs 1083.3 +/- 155.5 micrograms Ang I/g/hr, N.S.). On the other hand, both captopril and perindopril decreased adrenal Ang II significantly (from 21.1 +/- 2.7 to 9.2 +/- 0.5 pg/capsule and from 15.5 +/- 2.9 to 2.0 +/- 0.6 pg/capsule, respectively). Adrenal renin was not altered by either treatment. In spite of no inhibition of plasma Ang II, the pressor response to intravenous Ang I was still suppressed after captopril treatment. Both captopril and perindopril lowered the blood pressure of the rats significantly. Our results support the hypothesis that inhibition of tissue RAS is important for the hypotensive action of ACE inhibition.
Tokita
Y
Y
Department of Medicine, Medical College of Ohio, Toledo 43699.
Oda
H
H
Franco-Saenz
R
R
Mulrow
P J
PJ
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D020913:Perindopril; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D000804:Angiotensin II; D002216:Captopril; D012083:Renin; D020913:Perindopril