![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 288, Issue 2, 742-751, February 1999
Departments of
Physiology (X.Z., F.A.R., R.B., X.X., T.H.H.) and
Pharmacology (A.N.), New York Medical College, Valhalla, New York
Increasing evidence suggests that angiotensin-converting enzyme (ACE)
inhibitors can increase vascular nitric oxide (NO) production. Recent
studies have found that combined inhibition of ACE and neutral
endopeptidase (NEP) may have a greater beneficial effect in the
treatment of heart failure than inhibition of ACE alone. Amlodipine, a
calcium channel antagonist, has also been reported to have a favorable
effect in the treatment of patients with cardiac dysfunction. The
purpose of this study was to determine whether and the extent to which
all of these agents used in the treatment of heart failure stimulate
vascular NO production. Heart failure was induced by rapid ventricular
pacing in conscious dogs. Coronary microvessels were isolated from
normal and failing dog hearts. Nitrite, the stable metabolite of NO,
was measured by the Griess reaction. ACE and NEP inhibitors and
amlodipine significantly increased nitrite production from coronary
microvessels in both normal and failing dog hearts. However, nitrite
release was reduced after heart failure. For instance, the highest
concentration of enalaprilat, thiorphan, and amlodipine increased
nitrite release from 85 ± 4 to 156 ± 9, 82 ± 7 to
139 ± 8, and 74 ± 4 to 134 ±10 pmol/mg (all
*p < .01 versus control), respectively, in normal dog hearts. Nitrite release in response to the highest concentration of
these two inhibitors and amlodipine was reduced by 41% and 31% and
32% (all #p < .01 versus normal), respectively,
in microvessels after heart failure. The increase in nitrite induced by
either ACE or NEP inhibitors or amlodipine was entirely abolished by Nw-nitro-L-arginine methyl
ester, HOE 140 (a B2-kinin receptor antagonist), and
dichloroisocoumarin (a serine protease inhibitor) in both groups. Our
results indicate that: 1) there is an impaired endothelial NO
production after pacing-induced heart failure; 2) both ACE and NEP are
largely responsible for the metabolism of kinins and modulate canine
coronary NO production in normal and failing heart; and 3) amlodipine
releases NO even after heart failure and this may be partly responsible
for the favorable effect of amlodipine in the treatment of heart
failure. Thus, the restoration of reduced coronary vascular NO
production may contribute to the beneficial effects of these agents in
the treatment of heart failure.
This article has been cited by other articles:
|
|
 |
|
  D. Ianzer, R. A. S. Santos, G. M. Etelvino, C. H. Xavier, J. de Almeida Santos, E. P. Mendes, L. T. Machado, B. C. Prezoto, V. Dive, and A. C. M. de Camargo Do the Cardiovascular Effects of Angiotensin-Converting Enzyme (ACE) I Involve ACE-Independent Mechanisms? New Insights from Proline-Rich Peptides of Bothrops jararaca J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 795 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-P. Zhang and T. H. Hintze cAMP signal transduction induces eNOS activation by promoting PKB phosphorylation Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2376 - H2384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schulz, M. Kelm, and G. Heusch Nitric oxide in myocardial ischemia/reperfusion injury Cardiovasc Res, February 15, 2004; 61(3): 402 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.P. Mason, P. Marche, and T.H. Hintze Novel Vascular Biology of Third-Generation L-Type Calcium Channel Antagonists: Ancillary Actions of Amlodipine Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2155 - 2163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-P. Zhang, H. Tada, Z. Wang, and T. H. Hintze cAMP Signal Transduction, A Potential Compensatory Pathway for Coronary Endothelial NO Production After Heart Failure Arterioscler. Thromb. Vasc. Biol., August 1, 2002; 22(8): 1273 - 1278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Nikolaidis, A. Doverspike, R. Huerbin, T. Hentosz, and R. P. Shannon Angiotensin-Converting Enzyme Inhibitors Improve Coronary Flow Reserve in Dilated Cardiomyopathy by a Bradykinin-Mediated, Nitric Oxide-Dependent Mechanism Circulation, June 11, 2002; 105(23): 2785 - 2790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Oikawa, K. Maehara, T. Saito, K. Tamagawa, and Y. Maruyama Attenuation of angiotensin II-mediated coronary vasoconstriction and vasodilatory action of angiotensin-converting enzyme inhibitor in pacing-induced heart failure in dogs J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1188 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-p. Sun, B.-q. Zhu, A. E. M. Browne, S. Pulukurthy, T. M. Chou, K. Sudhir, S. A. Glantz, P. C. Deedwania, K. Chatterjee, and W. W. Parmley Comparative Effects of ACE Inhibitors and an Angiotensin Receptor Blocker on Atherosclerosis and Vascular Function Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2001; 6(2): 175 - 181. [Abstract] [PDF]
|
|
|
|
|
|
Y.-T. Shen, P. S Buie, J. J Lynch, S. M Krause, and X.-L. Ma Chronic therapy with an ETA/B receptor antagonist in conscious dogs during progression of congestive heart failure: Intracellular Ca2+ regulation and nitric oxide mediated coronary relaxation Cardiovasc Res, November 1, 2000; 48(2): 332 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Recchia, T. R. Vogel, and T. H. Hintze NO metabolites accumulate in erythrocytes in proportion to carbon dioxide and bicarbonate concentration Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H852 - H856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Recchia, P. I. McConnell, K. E. Loke, X. Xu, M. Ochoa, and T. H. Hintze Nitric oxide controls cardiac substrate utilization in the conscious dog Cardiovasc Res, November 1, 1999; 44(2): 325 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Berkels, A. Mueller, R. Roesen, and W. Klaus Nifedipine and Bay K 8644 Induce an Increase of [Ca2+] i and Nitric Oxide in Endothelial Cells Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(3): 175 - 181. [Abstract] [PDF]
|
|
|
|
 |
|
 X.-P. Yang, Y.-H. Liu, D. Mehta, M. A. Cavasin, E. Shesely, J. Xu, F. Liu, and O. A. Carretero Diminished Cardioprotective Response to Inhibition of Angiotensin-Converting Enzyme and Angiotensin II Type 1 Receptor in B2 Kinin Receptor Gene Knockout Mice Circ. Res., May 25, 2001; 88(10): 1072 - 1079. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
