Tissue-specific regulation of angiotensin-converting enzyme by angiotensin II and losartan in the rat.
Angiotensin II (Ang II) may regulate the release of components of the renin-angiotensin system in a tissue-specific manner. In order to study: (1) the effect of Ang II on gene expression and tissue levels of angiotensin-converting enzyme (ACE), and (2) the mechanism of the possible Ang II effect, we treated normal rats with Ang II and Losartan, an angiotensin AT1-receptor antagonist. Forty normal rats received Ang II (n = 20) at a rate of 200 ng kg-1 min-1 or 0.9% NaCl (n = 20) subcutaneously for 3 days using osmotic Alzet minipumps. Ten rats in both groups received Losartan (15 mg kg-1 day-1) in their drinking water, while the rest received tap water. ACE activity and mRNA levels were measured from pulmonary, cardiac, and renal tissue. Ang II treatment resulted in significant increases in blood pressure and heart weight as well as an increase in plasma Ang II concentration and a decrease in plasma renin activity. Simultaneous treatment with Losartan reduced the Ang II-induced effects on blood pressure and heart weight, and attenuated the Ang II-induced decrease in plasma renin activity. Pulmonary ACE activity and mRNA levels decreased during Ang II treatment, and these effects were not modified by simultaneous treatment with Losartan. Cardiac and kidney ACE activities and mRNA levels did not change significantly during Ang II treatment, but Losartan increased cardiac ACE activity (and decreased pulmonary ACE activity). The data indicate that Ang II regulates gene expression and activity of ACE in a tissue-specific manner in the rat, an effect probably involving angiotensin receptor subtype(s) different from the AT1-receptor.
Metsärinne
K P
KP
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
Helin
K H
KH
Saijonmaa
O
O
Stewen
P
P
Sirviö
M L
ML
Fyhrquist
F Y
FY
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D009928:Organ Specificity; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D019808:Losartan