2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishiyama, A. Articles by Navar, L. G. Search for Related Content PubMed PubMed Citation Articles by Nishiyama, A. Articles by Navar, L. G.

Renal Interstitial Fluid Angiotensin I and Angiotensin II Concentrations during Local Angiotensin-Converting Enzyme Inhibition

Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana.

Correspondence to Dr. Akira Nishiyama, Department of Pharmacology, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Phone: 81-87-898-5111, ext. 2502; Fax: 81-87-891-2126; E-mail akira{at}kms.ac.jp

ABSTRACT. It was recently demonstrated that angiotensin II (AngII) concentrations in the renal interstitial fluid (RIF) of anesthetized rats were in the nanomolar range and were not reduced by intra-arterial infusion of an angiotensin-converting enzyme (ACE) inhibitor (enalaprilat). This study was performed to determine changes in RIF AngI and AngII concentrations during interstitial administration of ACE inhibitors (enalaprilat and perindoprilat). Studies were also performed to determine the effects of enalaprilat on the de novo formation of RIF AngII elicited by interstitial infusion of AngI. Microdialysis probes (cut-off point, 30,000 D) were implanted in the renal cortex of anesthetized rats and were perfused at 2 µl/min. The effluent dialysate concentrations of AngI and AngII were measured by RIA, and reported values were corrected for the equilibrium rates at this perfusion rate. Basal RIF AngI (0.74 ± 0.05 nM) and AngII (3.30 ± 0.17 nM) concentrations were much higher than plasma AngI and AngII concentrations (0.15 ± 0.01 and 0.14 ± 0.01 nM, respectively; n = 27). Interstitial infusion of enalaprilat through the microdialysis probe (1 or 10 mM in the perfusate; n = 5 and 8, respectively) significantly increased RIF AngI concentrations but did not significantly alter AngII concentrations. However, perindoprilat (10 mM in the perfusate, n = 7) significantly decreased RIF AngII concentrations by 22 ± 4% and increased RIF AngI concentrations. Interstitial infusion of AngI (100 nM in the perfusate, n = 7) significantly increased the RIF AngII concentration to 8.26 ± 0.75 nM, whereas plasma AngI and AngII levels were not affected (0.15 ± 0.02 and 0.14 ± 0.02 nM, respectively). Addition of enalaprilat to the perfusate (10 mM) prevented the conversion of exogenously added AngI. These results indicate that addition of AngI in the interstitial compartment leads to low but significant conversion to AngII via ACE activity (blocked by enalaprilat). However, the addition of ACE inhibitors directly into the renal interstitium, via the microdialysis probe, either did not reduce RIF AngII levels or reduced levels by a small fraction of the total basal level, suggesting that much of the RIF AngII is formed at sites not readily accessible to ACE inhibition or is formed via non-ACE-dependent pathways.

This article has been cited by other articles:

				H. Kobori, M. Nangaku, L. G. Navar, and A. Nishiyama The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease Pharmacol. Rev., September 1, 2007; 59(3): 251 - 287. [Abstract] [Full Text] [PDF]

				H. Takahashi, A. Ichihara, Y. Kaneshiro, K. Inomata, M. Sakoda, T. Takemitsu, A. Nishiyama, and H. Itoh Regression of Nephropathy Developed in Diabetes by (Pro)renin Receptor Blockade J. Am. Soc. Nephrol., July 1, 2007; 18(7): 2054 - 2061. [Abstract] [Full Text] [PDF]

				J. C. Q. Velez, A. M. Bland, J. M. Arthur, J. R. Raymond, and M. G. Janech Characterization of renin-angiotensin system enzyme activities in cultured mouse podocytes Am J Physiol Renal Physiol, July 1, 2007; 293(1): F398 - F407. [Abstract] [Full Text] [PDF]

				Y. Kaneshiro, A. Ichihara, M. Sakoda, T. Takemitsu, A.H.M. N. Nabi, M. N. Uddin, T. Nakagawa, A. Nishiyama, F. Suzuki, T. Inagami, et al. Slowly Progressive, Angiotensin II-Independent Glomerulosclerosis in Human (Pro)renin Receptor-Transgenic Rats J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1789 - 1795. [Abstract] [Full Text] [PDF]

				C. Ruster and G. Wolf Renin-Angiotensin-Aldosterone System and Progression of Renal Disease J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2985 - 2991. [Abstract] [Full Text] [PDF]

				A. Ichihara, Y. Kaneshiro, T. Takemitsu, M. Sakoda, T. Nakagawa, A. Nishiyama, H. Kawachi, F. Shimizu, and T. Inagami Contribution of Nonproteolytically Activated Prorenin in Glomeruli to Hypertensive Renal Damage J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2495 - 2503. [Abstract] [Full Text] [PDF]

				A. Ichihara, F. Suzuki, T. Nakagawa, Y. Kaneshiro, T. Takemitsu, M. Sakoda, A.H.M. N. Nabi, A. Nishiyama, T. Sugaya, M. Hayashi, et al. Prorenin Receptor Blockade Inhibits Development of Glomerulosclerosis in Diabetic Angiotensin II Type 1a Receptor-Deficient Mice J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1950 - 1961. [Abstract] [Full Text] [PDF]

				A. Ichihara, Y. Kaneshiro, T. Takemitsu, M. Sakoda, F. Suzuki, T. Nakagawa, A. Nishiyama, T. Inagami, and M. Hayashi Nonproteolytic Activation of Prorenin Contributes to Development of Cardiac Fibrosis in Genetic Hypertension Hypertension, May 1, 2006; 47(5): 894 - 900. [Abstract] [Full Text] [PDF]

				H. Kobori, Y. Ozawa, Y. Suzaki, and A. Nishiyama Enhanced Intrarenal Angiotensinogen Contributes to Early Renal Injury in Spontaneously Hypertensive Rats J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2073 - 2080. [Abstract] [Full Text] [PDF]

				N. Li, J. Zimpelmann, K. Cheng, J. A. Wilkins, and K. D. Burns The role of angiotensin converting enzyme 2 in the generation of angiotensin 1-7 by rat proximal tubules Am J Physiol Renal Physiol, February 1, 2005; 288(2): F353 - F362. [Abstract] [Full Text] [PDF]

				B. Rodriguez-Iturbe, N. D. Vaziri, J. Herrera-Acosta, and R. J. Johnson Oxidative stress, renal infiltration of immune cells, and salt-sensitive hypertension: all for one and one for all Am J Physiol Renal Physiol, April 1, 2004; 286(4): F606 - F616. [Abstract] [Full Text] [PDF]

				J. Stegbauer, V. Oberhauser, O. Vonend, and L. C. Rump Angiotensin-(1-7) modulates vascular resistance and sympathetic neurotransmission in kidneys of spontaneously hypertensive rats Cardiovasc Res, February 1, 2004; 61(2): 352 - 359. [Abstract] [Full Text] [PDF]

				W. A. Wilmer, B. H. Rovin, C. J. Hebert, S. V. Rao, K. Kumor, and L. A. Hebert Management of Glomerular Proteinuria: A Commentary J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3217 - 3232. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673