Generation of angiotensin II from human plasma by tissue kallikrein.
1. Human plasma was incubated with tissue kallikrein from porcine pancreas, dialysed to obtain a fraction with a molecular mass < 10 kDa and further purified by reverse-phase chromatography. 2. Vasopressor activity in the fractions obtained was tested in the isolated perfused rat kidney. 3. In one fraction a strong vasopressor action was found, which was blocked by saralasin and by an angiotensin II antibody. 4. Aprotinin inhibited the formation of vasopressor substances by tissue kallikrein. 5. U.v.-laser desorption/ionization mass spectrometry revealed a molecular mass of 1046 Da in the purified active fraction. 6. It is concluded that tissue kallikrein forms not only kinins, but also angiotensin II, from human plasma under physiological conditions.
Krivoy
N
N
Medicine A and Clinical Pharmacology Unit, Rambam Medical Center, Haifa, Israel.
Schlüter
H
H
Karas
M
M
Zidek
W
W
D000804:Angiotensin II / Q000097:blood*; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007610:Kallikreins / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply; D013058:Mass Spectrometry; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D012504:Saralasin / Q000494:pharmacology
D000804:Angiotensin II; D007611:Aprotinin; D007610:Kallikreins; D012504:Saralasin; D009638:Norepinephrine