Cardiac interstitial fluid levels of angiotensin I and II in the pig

Objective: To study whether cardiac interstitial fluid levels of angiotensi n 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 t o the interstitial fluid levels of these peptides. Design and methods: Microdialysis probes were placed in the left ventricula r (LV) myocardium of eight anaesthetized pigs, three of which were untreate d and five treated with the angiotensin II type 1 (AT(1)) receptor antagoni st L-158,809 (10 mg intracoronary), All pigs were given a 1 h intracoronary infusion of I-125-Ang II, Aortic and coronary venous blood samples were ta ken 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 I-125-Ang II. Aortic Ang I and II levels (22 and 16 fm ol/ml; geometric mean of eight pigs) were comparable to coronary venous Ang I and II levels, whereas the coronary venous I-125-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 animal s, the I-125-Ang II levels per g LV tissue were similar to the levels per m l coronary venous plasma, and the ex vivo half-life of tissue I-125-Ang II was > 30 min. In treated animals, tissue I-125-Ang II was < 5% of coronary venous I-125-Ang II and became undetectable within 15 min. I-125-Ang II, An g 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 a ll animals. Conclusions: Plasma and myocardial interstitial fluid angiotensin levels ar e 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 metabo lism in the vascular wall. Binding to AT(1) receptors protects Ang II again st metabolism. J Hypertens 1999, 17:1885-1891 (C) Lippincott Williams & Wil kins.