title: Perindoprilat changes ANG (1-9) production in renal arteries isolated from young spontaneously hypertensive rats after ANG I incubation.
abstract: We used mass spectrometry to quantitate production of angiotensinogen metabolites in renal artery of 3- and 7-month-old Wistar-Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR). Tissue fragments were incubated for 15 min in oxygenated buffer, with added angiotensin I. Concentrations of angiotensins I (ANG I), II (ANG II), III (ANG III), IV (ANG IV), angiotensin (1-9) [ANG (1-9)], angiotensin (1-7) [ANG (1-7)], and angiotensin (1-5) [ANG (1-5)], excreted into the buffer during experiment, were measured using liquid chromatography-mass spectrometry (LC/MS) and expressed per mg of dry tissue. Effects of pretreatment with 10 microM perindoprilat on the production of ANG I metabolites were quantitated. Background production of any of ANG I metabolites differed neither between WKY and SHR rats nor between 3- and 7-month-old rats. Perindoprilat pretreatment of renal arteries resulted, as expected, in decrease of ANG II production. However, renal arteries of 7-month-old SHR rats were resistant to ACE inhibitor and did not change ANG II production in response to perindoprilat. In renal arteries, taken from 3-month-old rats, pretreated with perindoprilat, incubation with ANG I, resulted in the level of ANG (1-9) significantly higher in SHR than WKY rats. Our conclusion is that in SHR rats, sensitivity of renal artery ACE to perindoprilat inhibition changes with age.
authors.affiliation: Department of Pharmacology, Jagiellonian University Medical College, Kraków, Poland. Pawel.Wolkow@uj.edu.pl.
authors.forename: P P
authors.initials: PP
authors.lastname: Wołkow
authors.forename: B
authors.initials: B
authors.lastname: Bujak-Giżycka
authors.forename: J
authors.initials: J
authors.lastname: Jawień
authors.forename: R
authors.initials: R
authors.lastname: Olszanecki
authors.forename: J
authors.initials: J
authors.lastname: Madej
authors.forename: J
authors.initials: J
authors.lastname: Rutowski
authors.forename: R
authors.initials: R
authors.lastname: Korbut
mesh_terms: D000375:Aging / Q000378:metabolism; D000803:Angiotensin I / Q000378:metabolism*; D000818:Animals; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007211:Indoles; D010446:Peptide Fragments; C506331:angiotensin I (1-9); C053500:perindoprilat; D000803:Angiotensin I