From the Departments of Internal Medicine I (L.M. de L., A.M.B.B.,
M.A.D.H.S.) and Pharmacology (L.M. de L., A.H.J.D., P.R.S.), Erasmus
University Rotterdam, The Netherlands.
Correspondence to A.H. Jan Danser, PhD, Department of Pharmacology, Room EE 1418b, Erasmus University, Dr Molewaterplein 50, 3015 GE Rotterdam, Netherlands.
Abstract—We used a modification of
the isolated perfused rat heart, in which coronary effluent and
interstitial transudate were separately collected, to
investigate the localization and production of
angiotensin II (Ang II) in the heart. During combined renin
(0.7 to 1.5 pmol Ang I/mL per minute) and angiotensinogen
(6 to 12 pmol/mL) perfusion (4 to 8 mL/min) for 60 minutes (n=3), the
steady-state levels of Ang II in interstitial transudate in
two consecutive 10-minute periods were 4.3±1.5 and 3.6±1.5 fmol/mL
compared with 1.1±0.4 and 1.1±0.6 fmol/mL in coronary
effluent (mean±half range). During perfusion with Ang II (n=5),
steady-state Ang II in interstitial transudate was 32±19%
of arterial Ang II compared with 65±16% in
coronary effluent (mean±SD, P<.02). During
perfusion with Ang I (n=5), Ang II in interstitial
transudate was 5.1±0.6% of arterial Ang I compared with
2.2±0.3% in coronary effluent (P<.05). The
tissue concentration of Ang II in the combined
renin/angiotensinogen perfusions (per gram) was as high as
the concentration in interstitial transudate (per
milliliter). Addition of losartan (10-6 mol/L) to
the renin/angiotensinogen perfusion (n=3) had no
significant effect on the tissue level of Ang II, whereas
losartan in the perfusions with Ang I (n=5) or Ang II (n=5)
decreased tissue Ang II to undetectably low levels. The results
indicate that the heart is capable of producing Ang II and that this
can lead to higher levels in tissue than in blood plasma. Cardiac Ang
II does not appear to be restricted to the extracellular fluid. This is
in part due to AT1-receptor–mediated cellular uptake of
extracellular Ang II, but our results also raise the possibility of
intracellular Ang II production.
© 1998 American Heart Association, Inc.
Scientific Contributions
Localization and Production of Angiotensin II in the Isolated Perfused Rat Heart
Key Words: angiotensin II • heart • receptors, angiotensin
This article has been cited by other articles:
 |
|
 |
|
  W. Chai, I. M. Garrelds, R. de Vries, and A.H. Jan Danser Cardioprotective Effects of Eplerenone in the Rat Heart: Interaction With Locally Synthesized or Blood-Derived Aldosterone? Hypertension, April 1, 2006; 47(4): 665 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Perry, C.-C. Wei, G. H. Hankes, S. R. Dillon, P. Rynders, R. Mukherjee, F. G. Spinale, and L. J. Dell'Italia Angiotensin II receptor blockade does not improve left ventricular function andremodeling in subacute mitral regurgitation in the dog J. Am. Coll. Cardiol., April 17, 2002; 39(8): 1374 - 1379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. F. Hilgers, R. Veelken, D. N. Muller, H. Kohler, A. Hartner, S. R. Botkin, C. Stumpf, R. E. Schmieder, and R. A. Gomez Renin Uptake by the Endothelium Mediates Vascular Angiotensin Formation Hypertension, August 1, 2001; 38(2): 243 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Neri Serneri, M. Boddi, L. Poggesi, I. Simonetti, M. Coppo, M. L. Papa, G. F. Lisi, M. Maccherini, R. Becherini, A. Boncompagni, et al. Activation of cardiac renin-angiotensin system in unstable angina J. Am. Coll. Cardiol., July 1, 2001; 38(1): 49 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Saris, F. H. M. Derkx, R. J. A. De Bruin, D. H. W. Dekkers, J. M. J. Lamers, P. R. Saxena, M. A. D. H. Schalekamp, and A. H. Jan Danser High-affinity prorenin binding to cardiac man-6-P/IGF-II receptors precedes proteolytic activation to renin Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1706 - H1715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. PRESCOTT, D. W. SILVERSIDES, S. M. L. CHIU, and T. L. REUDELHUBER Contribution of circulating renin to local synthesis of angiotensin peptides in the heart Physiol Genomics, November 9, 2000; 4(1): 67 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takeda, T. Yoneda, M. Demura, I. Miyamori, and H. Mabuchi Cardiac Aldosterone Production in Genetically Hypertensive Rats Hypertension, October 1, 2000; 36(4): 495 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, A. S. Clanachan, and B. I. Jugdutt Enhanced Expression of Angiotensin II Type 2 Receptor, Inositol 1,4,5-Trisphosphate Receptor, and Protein Kinase C{epsilon} During Cardioprotection Induced by Angiotensin II Type 2 Receptor Blockade Hypertension, October 1, 2000; 36(4): 506 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. van Kats, D. J. Duncker, D. B. Haitsma, M. P. Schuijt, R. Niebuur, R. Stubenitsky, F. Boomsma, M. A. D. H. Schalekamp, P. D. Verdouw, and A. H. J. Danser Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Blockade Prevent Cardiac Remodeling in Pigs After Myocardial Infarction : Role of Tissue Angiotensin II Circulation, September 26, 2000; 102(13): 1556 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. De Mello and A. H. J. Danser Angiotensin II and the Heart : On the Intracrine Renin-Angiotensin System Hypertension, June 1, 2000; 35(6): 1183 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mazzolai, T. Pedrazzini, F. Nicoud, G. Gabbiani, H.-R. Brunner, and J. Nussberger Increased Cardiac Angiotensin II Levels Induce Right and Left Ventricular Hypertrophy in Normotensive Mice Hypertension, April 1, 2000; 35(4): 985 - 991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Saris, M. A. van Dijk, I. Kroon, M. A. D. H. Schalekamp, and A. H. J. Danser Functional Importance of Angiotensin-Converting Enzyme-Dependent In Situ Angiotensin II Generation in the Human Forearm Hypertension, March 1, 2000; 35(3): 764 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.H.J. Danser, J. J Saris, M. P Schuijt, and J. P van Kats Is there a local renin--angiotensin system in the heart? Cardiovasc Res, November 1, 1999; 44(2): 252 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. MaassenVanDenBrink, R. de Vries, P. R. Saxena, M. A.D.H. Schalekamp, and A.H.J. Danser Vasoconstriction by in situ formed angiotensin II: role of ACE and chymase Cardiovasc Res, November 1, 1999; 44(2): 407 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Dostal and K. M. Baker The Cardiac Renin-Angiotensin System : Conceptual, or a Regulator of Cardiac Function? Circ. Res., October 1, 1999; 85(7): 643 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brunner Cardiac endothelin and big endothelin in right-heart hypertrophy due to monocrotaline-induced pulmonary hypertension in rat Cardiovasc Res, October 1, 1999; 44(1): 197 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C Wollert and H. Drexler The renin-angiotensin system and experimental heart failure Cardiovasc Res, September 1, 1999; 43(4): 838 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Muller, K. F. Hilgers, S. Mathews, V. Breu, W. Fischli, R. Uhlmann, and F. C. Luft Effects of Human Prorenin in Rats Transgenic for Human Angiotensinogen Hypertension, January 1, 1999; 33(1): 312 - 317. [Abstract] [Full Text] [PDF]
|
|