Enhancement of intrarenal angiotensin II levels in 2 kidney 1 clip and angiotensin II induced hypertension.
Previous studies have indicated that the hypertension that develops after unilateral arterial constriction (2 kidney, 1 clip) involves an active participation by the non-clipped contralateral kidney. Even though the non-clipped kidney is not the initial causative factors, and despite the progressive renin depletion during the early weeks following clipping, the non-clipped kidney is highly responsive to angiotensin blockers. Furthermore, the non-clipped kidney has augmented tissue ANG II levels and ACE activity suggesting that some renin-independent mechanism may be stimulating intrarenal ANG II formation. This model has been simulated by infusing ANG II at low subpressor doses (40 ng/min) to uninephrectomized rats for 14 days. With this model, plasma and renal renin levels are markedly suppressed; however, the renal ANG II levels are increased to levels above those that can be explained on the basis of circulating ANG II. In agreement with the responses observed in the non-clipped kidney of 2K1C rats, there is also an increased renal ACE activity. In contrast to the marked suppression of renin gene expression and renin activity, angiotensinogen gene expression is not suppressed. These results support the hypothesis that small elevations in circulating ANG II stimulate intrarenal ANG II production through a renin-independent mechanism.
Navar
L G
LG
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Von Thun
A M
AM
Zou
L
L
el-Dahr
S S
SS
Mitchell
K D
KD
D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D006978:Hypertension, Renovascular / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012083:Renin / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin