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Angiotensin II exerts positive feedback on the intrarenal renin-angiotensin system by an angiotensin converting enzyme-dependent mechanism.

AbstractBACKGROUND:
Plasma angiotensin II (ANG II) is not increased significantly in renovascular hypertension (RVH), but tissue ANG II levels are elevated in both kidneys of renovascular rats. Because the contralateral, non-ischemic kidney is critical for maintenance of hypertension in RVH, this study sought to understand the mechanism by which intrarenal ANG II levels are augmented in the non-ischemic kidney. This study tested the hypothesis that an incremental increase in plasma ANG II induces the intrarenal renin-angiotensin system (RAS) in the non-ischemic kidney by an angiotensin converting enzyme (ACE) dependent mechanism.
METHODS:
To simulate the incremental increase in plasma ANG II induced by the ischemic kidney in RVH, an ANG II infusion model was used. This model used a chronic infusion of ANG II (40 ng/min) or vehicle by osmotic minipump into uninephrectomized rats. Parallel groups were treated with the ACE inhibitor Enalaprilat (200 mg/kg/day). Intrarenal ACE activity was measured by radioenzymatic assay. ANG II levels were quantified by radioimmunoassay.
RESULTS:
Hypertension was evident in ANG II-infused rats, compared to control rats (155 +/- 4 versus 112 +/- 1 mmHg; P < 0.001). Concurrent treatment with Enalaprilat reversed the hypertension induced by ANG II infusion (98 +/- 3 versus 155 +/- 4 mmHg; P < 0.001). ANG II up-regulated intrarenal ACE activity in the non-ischemic kidney (59.2 +/- 11.9 versus 25.2 +/- 6.8 units/mg protein; P < 0.01). Enalaprilat significantly decreased renal ACE activity in ANG II-treated rats, compared to ANG II alone (11.4 +/- 1.0 versus 59.2 +/- 11.9 units/mg protein; P < 0.001). Intrarenal ANG II was increased in ANG II-infused rats, compared to control animals (52.9 +/- 7.1 versus 23.0 +/- 3.2 fmol/mg tissue; P < 0.001), and Enalaprilat prevented ANG II-induced increases in intrarenal ANG II (29.9 +/- 2.6 versus 52.9 +/- 7.1 fmol/mg tissue; P < 0.05).
CONCLUSION:
Incremental changes in plasma ANG II induce de novo production of ANG II in the non-ischemic kidney to augment intrarenal ANG II content. ACE inhibition blocks this positive feedback loop, suggesting that ANG II activates the intrarenal RAS by an ACE-dependent mechanism. The impact of ACE inhibition on blood pressure suggests that this feedback loop may be an important mechanism for maintenance of hypertension in RVH.
AuthorsJavid Sadjadi, Gerald L Kramer, Chun-Hua Yu, M Burress Welborn 3rd, J Gregory Modrall
JournalThe Journal of surgical research (J Surg Res) Vol. 129 Issue 2 Pg. 272-7 (Dec 2005) ISSN: 0022-4804 [Print] United States
PMID15992826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Vasoconstrictor Agents
  • Angiotensin II
  • Peptidyl-Dipeptidase A
Topics
  • Angiotensin II (blood, pharmacology)
  • Animals
  • Blood Pressure (drug effects, physiology)
  • Feedback, Physiological (drug effects, physiology)
  • Hypertension, Renal (chemically induced, metabolism)
  • Kidney (enzymology)
  • Peptidyl-Dipeptidase A (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Renin-Angiotensin System (drug effects, physiology)
  • Vasoconstrictor Agents (blood, pharmacology)

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