Angiotensin metabolism in rat stomach wall: prevalence of angiotensin-(1-7) formation.
Our view of renin-angiotensin system (RAS) has changed over the past two decades: new metabolites and pathways have been described; also the importance of local renin-angiotensin systems became more clearly understood. However, there is relatively scarce information about formation and action of angiotensin peptides in gastrointestinal tract, especially in the stomach. Here, using LC-ESI-MS method we assessed the metabolism of Ang I in organ bath of rat stomach wall. Additionally we compared the expression of mRNA of angiotensin converting enzymes (ACE, ACE2) and neprilysin (NEP) in the stomach, aorta and renal artery in rats. Despite, similar levels of expression of ACE and ACE2 mRNA in stomach wall, aorta and renal artery, the absolute amounts of main Ang I metabolites produced by stomach wall (in ng/mg of dry tissue) were much lower than that produced by aorta and renal artery. Also, the pattern of angiotensin I metabolites was different: opposite to aorta and renal artery, incubation of Ang I with stomach wall fragments resulted in predominant formation of Ang-(1-7) and relatively lower production of Ang II. In stomach wall both, perindoprilat and tiorphan decreased production of Ang II, but did not influence generation of Ang-(1-7). In conclusion, we identified Ang-(1-7) as the main product of Ang I conversion in rat stomach wall. The biological role of prevalence of Ang-(1-7) formation in stomach require further investigation.
Pharmacology, Jagiellonian University School of Medicine, 16 Grzegorzecka Street, Krakow, Poland. mfolszan@cyf-kr.edu.pl
R
R
Olszanecki
J
J
Madej
M
M
Suski
A
A
Gebska
B
B
Bujak-Gizycka
R
R
Korbut
D000803:Angiotensin I / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002853:Chromatography, Liquid; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation; D007211:Indoles / Q000494:pharmacology; D008297:Male; D015260:Neprilysin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D021241:Spectrometry, Mass, Electrospray Ionization; D015244:Thiorphan / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D010446:Peptide Fragments; D012333:RNA, Messenger; C053500:perindoprilat; D000803:Angiotensin I; D015244:Thiorphan; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D015260:Neprilysin; C118790:angiotensin I (1-7)