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
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