This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oikawa, Y. Articles by Maruyama, Y. Search for Related Content PubMed PubMed Citation Articles by Oikawa, Y. Articles by Maruyama, Y.

EXPERIMENTAL STUDY

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

^a First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan

Manuscript received January 2, 2001; revised manuscript received May 30, 2001, accepted June 19, 2001.

Reprint requests and correspondence: Dr. Yukio Maruyama, Professor and Chairman, First Department of Internal Medicine, Fukushima Medical University, Hikarigaoka-1, Fukushima 960-1295, Japan
maruyama{at}fmu.ac.jp

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 (AT₁R and AT₂R, respectively) antagonists in chronic heart failure (CHF).

BACKGROUND

Angiotensin II 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 AT₁R antagonist L158,809 or the AT₂R 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 mm 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 II did not change the slope or P_f = 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.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ANP = atrial natriuretic peptide   AT1R = angiotensin II type 1 receptor   AT2R = angiotensin II type 2 receptor   CHF = chronic heart failure   NE = norepinephrine   NO = nitric oxide   PFR = (coronary) pressure–flow relationship   Pf = 0 = zero-flow pressure

This article has been cited by other articles:

				D. J. Duncker and R. J. Bache Regulation of Coronary Blood Flow During Exercise Physiol Rev, July 1, 2008; 88(3): 1009 - 1086. [Abstract] [Full Text] [PDF]

				D. Merkus, D. B. Haitsma, O. Sorop, F. Boomsma, V. J. de Beer, J. M. J. Lamers, P. D. Verdouw, and D. J. Duncker Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2082 - H2089. [Abstract] [Full Text] [PDF]