Cardiac interstitial fluid levels of angiotensin I and II in the pig.
OBJECTIVE
To study whether cardiac interstitial fluid levels of angiotensin I and II (Ang I and II) can be monitored in vivo, using the microdialysis technique, and to assess the contribution of plasma-derived angiotensins to the interstitial fluid levels of these peptides.


METHODS
Microdialysis probes were placed in the left ventricular (LV) myocardium of eight anaesthetized pigs, three of which were untreated and five treated with the angiotensin II type 1 (AT1) receptor antagonist L-158,809 (10 mg intracoronary). All pigs were given a 1 h intracoronary infusion of 125I-Ang II. Aortic and coronary venous blood samples were taken under steady-state conditions, and interstitial dialysate was collected during the entire infusion period. Immediately after stopping the infusion, LV tissue pieces were obtained at various time points.


RESULTS
L-158,809 did not affect the levels of endogenous Ang I and II or the levels of plasma 125I-Ang II. Aortic Ang I and II levels (22 and 16 fmol/ml; geometric mean of eight pigs) were comparable to coronary venous Ang I and II levels, whereas the coronary venous 125I-Ang II levels (6650 c.p.m./ml) were approximately 30 times higher than those in the aorta. Tissue Ang I and II levels were 5 and 17 fmol/g, respectively. In untreated animals, the 125I-Ang II levels per g LV tissue were similar to the levels per ml coronary venous plasma, and the ex vivo half-life of tissue 1251-Ang II was > 30 min. In treated animals, tissue 125I-Ang II was < 5% of coronary venous 125I-Ang II and became undetectable within 15 min. 125I-Ang II, Ang I and Ang II levels in the interstitial fluid were close to or below the detection limit (200 c.p.m., 60 fmol and 20 fmol per ml, respectively) in all animals.


CONCLUSIONS
Plasma and myocardial interstitial fluid angiotensin levels are of the same order of magnitude. Plasma Ang II does not contribute to the interstitial fluid level of Ang II, most likely because of its rapid metabolism in the vascular wall. Binding to AT1 receptors protects Ang II against metabolism.
Schuijt
M P
MP
Cardiovascular Research Institute Erasmus University Rotterdam, The Netherlands.
van Kats
J P
JP
de Zeeuw
S
S
Duncker
D J
DJ
Verdouw
P D
PD
Schalekamp
M A
MA
Danser
A H
AH
D000803:Angiotensin I / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001011:Aorta; D003331:Coronary Vessels; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D017551:Microdialysis; D009206:Myocardium / Q000378:metabolism*; D013552:Swine
D000804:Angiotensin II; D000803:Angiotensin I