Myocardial Bradykinin Following Acute Angiotensin-Converting Enzyme Inhibition, AT1 Receptor Blockade, or Combined Inhibition in Congestive Heart Failure

Abstract

Background: The present study examined the effects of acute angiotensin-converting enzyme inhibition (ACEI), AT, receptor blockade (AT, block), or combined treatment on in vitro and in vivo bradykinin (BK) levels. Methods: BK levels were measured in isolated porcine myocyte preparations (n = 13) in the presence of exogenous BK (10-8 M); with an ACEI (benezaprilat; 0.1 mM) and BK; an AT, block (valsartan; 10-5 M) and BK; and combined treatment and BK. In a second study, myocardial microdialysis was used to measure porcine interstitial BK levels in both normal (n = 14) and pacing-induced congestive heart failure (CHF) (240 beats/min, 3 weeks, n = 16) under the following conditions: baseline, following ACEI (benezaprilat, 0.0625 mg/kg) or AT, block (valsartan, 0. I mg/kg), and a combined treatment (benezaprilat, 0.0625 mg/kg; valsartan, 0.1 mg/kg). Results: In the left ventricular myocyte study, BK levels increased over 93% with all treatments compared to untreated values (P < 0.05). In the in vivo study, basal interstitial BK values were lower in the CHF group than in controls (2.64 ± 0.57 vs 5.91 + 1.4 nM, respectively, P < 0.05). Following acute infusion of the ACEI, BK levels in the CHF state increased from baseline (57% ± 22; P < 0.05). Following combined ACEIIAT, block, BK levels increased from baseline in both control (42% ± 11) and CHF groups (60% ± 22; P < 0.05 for both). Conclusion: These findings suggest that ACEI, or combined ACEI/AT, block increased BK at the level of the myocyte and potentiated BK levels in the CHF myocardial interstitium.