Local angiotensin formation in hindlimbs of uremic hypertensive and renovascular hypertensive rats.
To examine and characterize the vascular renin--angiotensin system in low-renin models of renal hypertension with and without the presence of overt renal insufficiency, we studied the formation and metabolism of angiotensin in isolated perfused rat hindquarter preparations. Rats with 5/6 nephrectomy (5/6NX) and rats with one-kidney, one clip (1K1C) hypertension were compared to sham operated (sham) animals. Angiotensin peptides in plasma or perfusate were characterized by high-performance liquid chromatography and radioimmunoassay (RIA). Plasma angiotensin II was lower, and blood pressure was higher in both experimental groups, compared to sham animals. Plasma angiotensinogen, measured by both direct and indirect RIA, was increased in both experimental groups. The spontaneous release of angiotensin I and angiotensin II from perfused hindquarters did not differ between the groups. Angiotensin I conversion was not different in 5/6NX or 1K1C groups compared with controls. Furthermore, angiotensin conversion was completely inhibited by captopril (1 mumol/l) in all groups. Renin-induced angiotensin release was significantly increased in 5/6NX as compared with sham rats, whereas there was no difference in renin-induced angiotensin release between 1K1C and sham animals. Angiotensin II degradation was significantly attenuated in 5/6NX rats when compared with sham rats (27.6% versus 53.9%, respectively, P less than 0.05) but was unaltered in 1K1C rats. Thus, in chronic uremic hypertension, renin-induced angiotensin formation was increased in the face of decreased angiotensin II degradation. These data suggest that vascular angiotensin may contribute to the elevated blood pressure observed in chronic renal failure. In 1K1C rats, vascular angiotensin formation and metabolism was unchanged despite suppressed plasma angiotensin II.
Kuczera
M
M
Department of Medicine, University of Heidelberg, Federal Republic of Germany.
Hilgers
K F
KF
Lisson
C
C
Ganten
D
D
Hilgenfeldt
U
U
Ritz
E
E
Mann
J F
JF
D000804:Angiotensin II / Q000096:biosynthesis* / Q000378:metabolism; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006614:Hindlimb; D006977:Hypertension, Renal / Q000378:metabolism*; D006978:Hypertension, Renovascular / Q000378:metabolism*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D014511:Uremia / Q000378:metabolism*
D000808:Angiotensinogen; D000804:Angiotensin II; D012083:Renin