Losartan, a specific angiotensin II receptor antagonist, increases angiotensin I and angiotensin II release from isolated rat hind legs: evidence for locally regulated renin-angiotensin system in vascular tissue.
The effect of Losartan (10(-9) to 10(-6) M) on angiotensins I and II release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal and bilaterally nephrectomized rats. Losartan increased dramatically both angiotensins I (Ang I) and II (Ang II) release in a dose-dependent fashion; the maximal percent increment in Ang I and Ang II release evoked by Losartan (10(-6) M) was about +380% and +160%, respectively, in normal rat hind legs. In nephrectomized animals, Losartan elicited a marked increase in both peptides dose-dependently. There was a highly positive correlation between the released amounts of Ang I and that of Ang II altered by Losartan in either normal (r = 0.954) or nephrectomized rats (r = 0.923). These results not only confirm the existence of a functional renin-angiotensin system in vascular tissues, but also suggest that the system is regulated by locally generated Ang II.
Mizuno
K
K
Third Department of Internal Medicine, Fukushima Medical College, Japan.
Tani
M
M
Niimura
S
S
Sanada
H
H
Haga
H
H
Hashimoto
S
S
Watanabe
H
H
Ohtsuki
M
M
Fukuchi
S
S
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009392:Nephrectomy; D010477:Perfusion; D051381:Rats; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D000803:Angiotensin I; D019808:Losartan