Y. Oikawa et al., Attenuation of angiotensin II-mediated coronary vasoconstriction and vasodilatory action of angiotensin-converting, enzyme inhibitor in pacing-induced heart failure in dogs, J AM COL C, 38(4), 2001, pp. 1188-1194
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
OBJECTIVES We investigated the changes in coronary vascular resistance caus
ed by angiotensin II, angiotensin-converting enzyme (ACE) inhibition and an
giotensin 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 angio
tensin II in CHF might exert significant vasoconstriction. METHODS Eleven d
ogs were studied. Before and after three and five weeks of rapid pacing, co
ronary flow dynamics were evaluated by the coronary pressure-flow relations
hip (PFR) in long diastole, before and after intracoronary injection of ang
iotensin 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 o
f 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 angi
otensin 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.