Direct proof for local generation and release of angiotensin II in peripheral human vascular tissue.
Previously we reported that immunoreactive angiotensin II (Ang II) release from isolated perfused human umbilical veins was inhibited by the angiotensin-converting enzyme inhibitor captopril. To further investigate the mechanism by which Ang II is generated in the blood vessels of humans, we examined the effects of various inhibitors of the renin-angiotensin system (captopril, delapril, N-acetyl-pepstatin, and human renin inhibitor KRI-1314) on Ang II release from perfused human umbilical cord veins in vitro. Isolated human umbilical veins were perfused with Krebs-Ringer solution, and immunoreactive Ang II released into the perfusate was measured directly by using a Sep-Pak C18 cartridge connected to the perfusion system. Both captopril and delapril diacid (10(-9) to 5 x 10(-6) mol/L), an active metabolite of delapril hydrochloride, suppressed the Ang II release in a dose-dependent fashion; the maximal percent suppression of Ang II release evoked by these inhibitors (5 x 10(-6) mol/L) was 56% and 64%, respectively, for captopril and delapril. Both N-acetyl-pepstatin (10(-9) to 10(-5) mol/L) and KRI-1314 (10(-9) to 10(-6) mol/L) suppressed Ang II release in a dose-related manner. At a 10(-6) mol/L concentration, KRI-1314 produced a 74% reduction in the basal rate of Ang II release, and a reduction threefold greater than the maximal reduction in basal Ang II release produced by N-acetyl-pepstatin.(ABSTRACT TRUNCATED AT 250 WORDS)
Mizuno
K
K
Third Department of Internal Medicine, Fukushima Medical College, Japan.
Niimura
S
S
Tani
M
M
Haga
H
H
Inagami
T
T
Fukuchii
S
S
D000804:Angiotensin II / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010434:Pepsin A / Q000037:antagonists & inhibitors; D010436:Pepstatins / Q000494:pharmacology; D013997:Time Factors; D014471:Umbilical Veins / Q000187:drug effects* / Q000378:metabolism
D010436:Pepstatins; C014195:Streptomyces pepsin inhibitor; D000804:Angiotensin II; D002216:Captopril; D010434:Pepsin A