Effects of intravenous urocortin on angiotensin-converting enzyme in rats.
We investigated the relationship between urocortin and the activity of angiotensin-converting enzyme (ACE), which plays a key role in producing the potent vasoconstrictor angiotensin II (Ang II). Urocortin was acutely and subchronically administered to Sprague-Dawley (SD) rats and then the serum and tissue (lung and aorta) ACE levels were evaluated. The tissue ACE mRNA was determined by using reverse transcription and polymerase chain reaction (RT-PCR) analysis. Immunofluorescence studies were also preformed to evaluate the effect of urocortin on ACE in cultured rat aortic endothelial cells (RAECs). Urocortin decreased the serum ACE level 1h after administration, whereas tissue ACE immunoreactivity and mRNA did not change. The prolonged administration of urocortin enhanced tissue ACE activity but the serum ACE level remained low. RT-PCR analysis showed that tissue ACE mRNA was elevated. Immunofluorescence studies also demonstrated an increase of ACE intensity in RAECs exposed to urocortin for 72 h. Corticotropin-releasing factor (CRF) receptor blocker, astressin, abolished the effects of urocortin. Extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker, PD98059, also markedly inhibited these effects, suggesting urocortin affects the activity of ACE through the ERK1/2 pathway in rats. These findings support the changes in mean arterial pressure (MAP) following acute and subchronic injections of urocortin in previous studies. Thus, the changes of the ACE activity and its production of Ang II may play a role in the vasodilatory property of urocortin.
Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
Cui
C
Yang
Yinyan
Y
Xu
Tavis
T
Mendez
Fang
F
Wang
Qin
Q
Yang
Shengnan
S
Li
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D054832:Urocortins; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D005419:Flavonoids; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D054832:Urocortins; D014665:Vasodilator Agents; C104416:astressin; D003346:Corticotropin-Releasing Hormone; D002216:Captopril; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D007703:Peptidyl-Dipeptidase A; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one