Attenuation of angiotensin II-mediated coronary vasoconstriction and vasodilatory action of angiotensin-converting, enzyme inhibitor in pacing-induced heart failure in dogs

OBJECTIVES We investigated the changes in coronary vascular resistance caused by angiotensin II, angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 or 2 receptor (AT,R and ATR, respectively) antagonists in chronic heart failure (CHF). BACKGROUND Angiotensin H is an intense vasoconstrictor, and increased angiotensin II in CHF might exert significant vasoconstriction. METHODS Eleven dogs were studied. Before and after three and five weeks of rapid pacing, coronary flow dynamics were evaluated by the coronary pressure-flow relationship (PFR) in long diastole, before and after intracoronary injection of angiotensin II, the ACE inhibitor enalaprilat, the AT(1)R antagonist L158,809 or the AT(2)R antagonist PD123319. RESULTS Before rapid pacing, angiotensin II reduced the slope of PFR (1.16 +/- 0.08 to 0.81 +/- 0,07 ml/min/100 g left ventricular mass per min Hg; p < 0.01) and increased the perfusion pressure at which coronary flow ceased (zero-flow pressure [P-f = 0]), whereas enalaprilat did not change either of them. After rapid pacing, angiotensin H did not change the slope or P-f = 0 0. In contrast, enalaprilat increased the slope (three weeks: 1.20 +/- 0.05 to 1.50 +/- 0.03; five weeks: 1.25 +/- 0.19 to 1.37 +/- 0.08; both p < 0.05) and decreased P-f = 0 after three weeks of pacing, but not after five weeks. Pretreatment with the bradykinin antagonist HOE-140 attenuated the enalaprilat-induced increase in coronary blood flow. L158,809 and PD123319 had no effect both before and after rapid pacing. CONCLUSIONS This suggests that the coronary vasoconstrictive effect of angiotensin II would disappear and the vasodilatory effect of the ACE inhibitor, partly through bradykinin, would be enhanced in the early stage of CHF. (C) 2001 by the American College of Cardiology.