(Circulation. 1995;92:2660-2665.)
© 1995 American Heart Association, Inc.
Articles |
Enhancement of Left Ventricular Relaxation in the Isolated Heart by an Angiotensin-Converting Enzyme Inhibitor
From the Cardiovascular Sciences Research Group, Departments of Pharmacology and Therapeutics (P.B.A., M.J.L.) and Cardiology (R.M.G.-M., A.M.S.), University of Wales College of Medicine, Cardiff, UK.
Correspondence to Dr A.M. Shah, Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK.
Background ACE inhibitors exert both acute and chronic beneficial effects on cardiac function (eg, remodeling, diastolic dysfunction) in experimental studies and in patients. They inhibit the formation of angiotensin II as well as the degradation of endogenous bradykinin. We recently reported that bradykinin induces selective left ventricular (LV) relaxant effects in isolated hearts via the release of nitric oxide. The present study examined the direct effects of interaction between the ACE inhibitor captopril and endogenous bradykinin on cardiac contractile function.
Methods and Results Isolated ejecting guinea pig hearts were studied under conditions of constant loading and heart rate. LV pressure was monitored by a 2F micromanometer-tipped catheter. Captopril (1 µmol/L, n=9) caused a progressive acceleration of LV relaxation without significantly affecting early systolic parameters (eg, LV dP/dtmax) or coronary flow. These effects were inhibited by the nitric oxide scavenger hemoglobin (1 µmol/L, n=5) or by the B2-kinin receptor antagonist HOE140 (10 nmol/L, n=5). In the presence of captopril, bradykinin (0.1 nmol/L, n=6) markedly accelerated LV relaxation (significantly more than captopril alone), whereas bradykinin alone (0.1 nmol/L, n=6) had no effect.
Conclusions These data indicate that the ACE inhibitor captopril causes an acute and selective enhancement of LV relaxation independent of changes in coronary flow, probably via an endogenous bradykinin/nitric oxide pathway.
Key Words: angiotensin • bradykinin • ventricles
This article has been cited by other articles:
 |
|
 |
|
  M. Seddon, A. M. Shah, and B. Casadei Cardiomyocytes as effectors of nitric oxide signalling Cardiovasc Res, July 15, 2007; 75(2): 315 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Funabiki, K. Onishi, K. Dohi, T. Koji, K. Imanaka-Yoshida, M. Ito, H. Wada, N. Isaka, T. Nobori, and T. Nakano Combined angiotensin receptor blocker and ACE inhibitor on myocardial fibrosis and left ventricular stiffness in dogs with heart failure Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2487 - H2492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Hamlin, P. S. Villars, J. T. Kanusky, and A. D. Shaw Role of Diastole in Left Ventricular Function, II: Diagnosis and Treatment Am. J. Crit. Care., November 1, 2004; 13(6): 453 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Brutsaert Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity Physiol Rev, January 1, 2003; 83(1): 59 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fujii, A. Wada, T. Tsutamoto, M. Ohnishi, T. Isono, and M. Kinoshita Bradykinin Improves Left Ventricular Diastolic Function Under Long-Term Angiotensin-Converting Enzyme Inhibition in Heart Failure Hypertension, May 1, 2002; 39(5): 952 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Bell, S. I. Mosfer, D. Lang, F. Donaldson, and M. J. Lewis Vitamin C and quinapril abrogate LVH and endothelial dysfunction in aortic-banded guinea pigs Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1704 - H1710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Dell’Italia and S. Oparil Bradykinin in the Heart : Friend Or Foe? Circulation, December 7, 1999; 100(23): 2305 - 2307. [Full Text] [PDF]
|
|
|
|
|
|
W. J Paulus and A. M Shah NO and cardiac diastolic function Cardiovasc Res, August 15, 1999; 43(3): 595 - 606. [Full Text] [PDF]
|
|
|
|
|
|
P. B. Anning, B. D. Prendergast, P. A. MacCarthy, A. M. Shah, D. C. Buss, and M. J. Lewis ATP is involved in myocardial and vascular effects of exogenous bradykinin in ejecting guinea pig heart Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H818 - H825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, F. Kajiya, H. Vink, I. Vergroesen, J. Dankelman, M. Goto, and J. A. E. Spaan Prolonged Diastolic Time Fraction Protects Myocardial Perfusion When Coronary Blood Flow Is Reduced Circulation, July 6, 1999; 100(1): 75 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lang, J. P Bell, U. Bayraktutan, G. R Small, A. M Shah, and M. J Lewis Phenotypic changes in rat and guinea pig coronary microvascular endothelium after culture: loss of nitric oxide synthase activity Cardiovasc Res, June 1, 1999; 42(3): 794 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Matter, L. Mandinov, P. A. Kaufmann, G. Vassalli, Z. Jiang, and O. M. Hess Effect of NO Donors on LV Diastolic Function in Patients With Severe Pressure-Overload Hypertrophy Circulation, May 11, 1999; 99(18): 2396 - 2401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Ritchie, R. J. Schiebinger, M. C. Lapointe, and J. D. Marsh Angiotensin II-induced hypertrophy of adult rat cardiomyocytes is blocked by nitric oxide Am J Physiol Heart Circ Physiol, October 1, 1998; 275(4): H1370 - H1374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bartunek, S. Dempsey, E. O. Weinberg, N. Ito, M. Tajima, S. Rohrbach, and B. H. Lorell Chronic L-arginine treatment increases cardiac cyclic guanosine 5'-monophosphate in rats with aortic stenosis: effects on left ventricular mass and beta-adrenergic contractile reserve J. Am. Coll. Cardiol., August 1, 1998; 32(2): 528 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D Prendergast, P. B Anning, M. J Lewis, and A. M Shah Regulation of left ventricular relaxation in the isolated guinea-pig heart by endogenous endothelin Cardiovasc Res, January 1, 1997; 33(1): 131 - 138. [Abstract] [Full Text] [PDF]
|
|