Regulation of vascular angiotensin release.
To investigate the regulatory mechanism of the vascular renin-angiotensin system, we perfused isolated rat hind legs with plasma-free buffer and quantified angiotensin peptides in the perfusate. Angiotensin release from hind legs was increased in rats pretreated with losartan (DuP 753) and rats fed a low sodium diet with subsequent furosemide and was decreased in nephrectomized rats and rats given dexamethasone, ethynylestradiol, and triiodothyronine. Using these models, we have attempted to identify which step or component of angiotensin metabolism determines angiotensin release level. Changes caused by these manipulations in plasma renin concentration and basal angiotensin release from hind legs were almost parallel, whereas plasma angiotensinogen concentration and the angiotensin release changed in opposite directions. Infusion of renin in hind legs caused a marked increase in angiotensin release and continued even 1 hour after cessation of renin infusion. Infusion of angiotensinogen did not alter the angiotensin release. Angiotensin clearance and angiotensin I conversion were not affected by either nephrectomy or losartan pretreatment. Aortic renin messenger RNA level was extremely low and not increased by nephrectomy or losartan pretreatment, although kidney renin messenger RNA level was increased by losartan pretreatment. These results provide evidence that plasma renin of kidney origin is the major source of vascular functional renin and plays the determining role in the regulation of vascular angiotensin release. Plasma-derived or locally produced angiotensinogen, locally produced renin, converting enzyme, and angiotensin clearance are not considered to be the primary determinant in the regulation of vascular angiotensin release in these acute and subacute experimental models.
Kato
H
H
Department of Biochemistry and Hypertension Center, Vanderbilt University School of Medicine, Nashville, TN 37232.
Iwai
N
N
Inui
H
H
Kimoto
K
K
Uchiyama
Y
Y
Inagami
T
T
D000803:Angiotensin I / Q000097:blood*; D000804:Angiotensin II / Q000097:blood*; D057911:Angiotensin Receptor Antagonists; D000808:Angiotensinogen / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009132:Muscles / Q000098:blood supply; D009392:Nephrectomy; D009838:Oligodeoxyribonucleotides; D010477:Perfusion; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D013777:Tetrazoles; D014284:Triiodothyronine; D000808:Angiotensinogen; D000804:Angiotensin II; D004997:Ethinyl Estradiol; D003907:Dexamethasone; D000803:Angiotensin I; D012083:Renin; D019808:Losartan