Tolerance to intravenous nitroglycerin in patients with congestive heart failure: role of increased intravascular volume, neurohumoral activation and lack of prevention with N-acetylcysteine
J Dupuis,
G Lalonde,
R Lemieux,
and
JL Rouleau
Division of Cardiology, Hopital du Sacre-Coeur de Montreal, Quebec, Canada.
To better understand the mechanism of nitrate tolerance in patients with congestive heart failure, 13 patients received a 24 h infusion of nitroglycerin (1.5 micrograms/kg body weight per min) with or without N-acetylcysteine (225 mg/kg per 24 h). The infusions were separated by a 24 h nitrate-free interval. By the end of the nitroglycerin infusion, mean arterial pressure had returned to baseline values and there was a significant increase in ventricular filling pressures and systemic vascular resistance compared with values after 1 h of treatment. The simultaneous infusion of N-acetylcysteine had no effect on these changes. Although a strict fluid restriction of 1.5 liters/day was maintained for 1 week before and throughout the study, after 24 h of nitroglycerin infusion there was a significant and similar degree of hemodilution whether nitroglycerin was infused alone (9.1 +/- 4.3%) or with N-acetylcysteine (8.7 +/- 4.1%). This hemodilution corresponded to an increase in intravascular volume of 745 +/- 382 ml, most of which occurred during the 1st h. Plasma renin activity increased and plasma atrial natriuretic peptide decreased during the infusion. The results of this study suggest that nitrate tolerance is multifactorial. In addition to the previously described pharmacologic tolerance to the effect of nitroglycerin on vascular smooth muscle, a capillary fluid shift from the extravascular to intravascular space appears to be involved, especially during the 1st h of the infusion. A third mechanism, reflex neurohumoral activation, also seems to contribute to the genesis of nitroglycerin tolerance.
This article has been cited by other articles:
|
|
|
|
 
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al.
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
J. Am. Coll. Cardiol.,
April 14, 2009;
53(15):
e1 - e90.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jessup, W. T. Abraham, D. E. Casey, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. A. Konstam, D. M. Mancini, P. S. Rahko, M. A. Silver, et al.
2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
J. Am. Coll. Cardiol.,
April 14, 2009;
53(15):
1343 - 1382.
[Full Text]
[PDF]
|
|
|
|
|
|
|
2009 WRITING GROUP TO REVIEW NEW EVIDENCE AND UPDA, M. Jessup, W. T. Abraham, D. E. Casey, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. A. Konstam, D. M. Mancini, P. S. Rahko, et al.
2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
Circulation,
April 14, 2009;
119(14):
1977 - 2016.
[Full Text]
[PDF]
|
|
|
|
|
|
|
2005 WRITING COMMITTEE MEMBERS, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, et al.
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
Circulation,
April 14, 2009;
119(14):
e391 - e479.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Fukatsu, T. Hayashi, A. Miyazaki-Akita, H. Matsui-Hirai, Y. Furutate, A. Ishitsuka, Y. Hattori, and A. Iguchi
Possible usefulness of apocynin, an NADPH oxidase inhibitor, for nitrate tolerance: prevention of NO donor-induced endothelial cell abnormalities
Am J Physiol Heart Circ Physiol,
July 1, 2007;
293(1):
H790 - H797.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. MacPherson, T. D. Gillespie, H. A. Dunkerley, D. H. Maurice, and B. M. Bennett
Inhibition of Phosphodiesterase 5 Selectively Reverses Nitrate Tolerance in the Venous Circulation
J. Pharmacol. Exp. Ther.,
April 1, 2006;
317(1):
188 - 195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Parent, N. Leblanc, and M. Lavallee
Nitroglycerin reduces myocardial oxygen consumption during exercise despite vascular tolerance
Am J Physiol Heart Circ Physiol,
March 1, 2006;
290(3):
H1226 - H1234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Munzel, A. Daiber, and A. Mulsch
Explaining the Phenomenon of Nitrate Tolerance
Circ. Res.,
September 30, 2005;
97(7):
618 - 628.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Elkayam, F. Bitar, M. W. Akhter, S. Khan, S. Patrus, and M. Derakhshani
Intravenous Nitroglycerin in the Treatment of Decompensated Heart Failure: Potential Benefits and Limitations
Journal of Cardiovascular Pharmacology and Therapeutics,
October 1, 2004;
9(4):
227 - 241.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. D. Horowitz
Amelioration of nitrate tolerance: matching strategies with mechanisms
J. Am. Coll. Cardiol.,
June 4, 2003;
41(11):
2001 - 2003.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Gori, J. S. Floras, and J. D. Parker
Effects of nitroglycerin treatment on baroreflex sensitivity andshort-term heart rate variability in humans
J. Am. Coll. Cardiol.,
December 4, 2002;
40(11):
2000 - 2005.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Gori and J. D. Parker
Nitrate Tolerance: A Unifying Hypothesis
Circulation,
November 5, 2002;
106(19):
2510 - 2513.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Gori and J. D. Parker
The Puzzle of Nitrate Tolerance: Pieces Smaller Than We Thought?
Circulation,
October 29, 2002;
106(18):
2404 - 2408.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kanamasa, T. Hayashi, A. Kimura, A. Ikeda, K. Ishikawa, and secondary prevention group
Long-term, Continuous Treatment with Both Oral and Transdermal Nitrates Increases Cardiac Events in Healed Myocardial Infarction Patients
Angiology,
July 1, 2002;
53(4):
399 - 408.
[Abstract]
[PDF]
|
|
|
|
|
|
|
N. Abdelaziz, F. Colombo, I. Mercier, and A. Calderone
Nitric Oxide Attenuates the Expression of Transforming Growth Factor-{beta}3 mRNA in Rat Cardiac Fibroblasts via Destabilization
Hypertension,
August 1, 2001;
38(2):
261 - 266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Hebert and J. Y. T. Lam
Nitroglycerin rebound associated with vascular, rather than platelet, hypersensitivity
J. Am. Coll. Cardiol.,
December 1, 2000;
36(7):
2311 - 2316.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kurz, U. Hink, G. Nickenig, A. B. Borthayre, D. G. Harrison, and T. Munzel
Evidence for a Causal Role of the Renin-Angiotensin System in Nitrate Tolerance
Circulation,
June 22, 1999;
99(24):
3181 - 3187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Watanabe, M. Kakihana, S. Ohtsuka, and Y. Sugishita
Randomized, double-blind, placebo-controlled study of carvedilol on the prevention of nitrate tolerance in patients with chronic heart failure
J. Am. Coll. Cardiol.,
November 1, 1998;
32(5):
1194 - 1200.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Watanabe, M. Kakihana, S. Ohtsuka, and Y. Sugishita
Preventive effects of carvedilol on nitrate tolerance--a randomized, double-blind, placebo-controlled comparative study between carvedilol and arotinolol
J. Am. Coll. Cardiol.,
November 1, 1998;
32(5):
1201 - 1206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Zanzinger, J. Czachurski, and H. Seller
Impaired Modulation of Sympathetic Excitability by Nitric Oxide After Long-term Administration of Organic Nitrates in Pigs
Circulation,
June 16, 1998;
97(23):
2352 - 2358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Parker and J. O. Parker
Nitrate Therapy for Stable Angina Pectoris
N. Engl. J. Med.,
February 19, 1998;
338(8):
520 - 531.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Hebert, J.-X. Xiang, and J. Y.T. Lam
Persistent Inhibition of Platelets During Continuous Nitroglycerin Therapy Despite Hemodynamic Tolerance
Circulation,
March 4, 1997;
95(5):
1308 - 1313.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. D. Parker, A. B. Parker, B. Farrell, and J. O. Parker
The Effect of Hydralazine on the Development of Tolerance to Continuous Nitroglycerin
J. Pharmacol. Exp. Ther.,
February 1, 1997;
280(2):
866 - 875.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. Munzel and E. Bassenge
Long-term Angiotensin-Converting Enzyme Inhibition With High-Dose Enalapril Retards Nitrate Tolerance in Large Epicardial Arteries and Prevents Rebound Coronary Vasoconstriction In Vivo
Circulation,
June 1, 1996;
93(11):
2052 - 2058.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. D. Parker, A. B. Parker, B. Farrell, and J. O. Parker
Effects of Diuretic Therapy on the Development of Tolerance to Nitroglycerin and Exercise Capacity in Patients With Chronic Stable Angina
Circulation,
February 15, 1996;
93(4):
691 - 696.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. Abrams
The Role of Nitrates in Coronary Heart Disease
Arch Intern Med,
February 27, 1995;
155(4):
357 - 364.
[Abstract]
[PDF]
|
|
|
|
|
|
|
U. Thadani
Nitrate Therapy and the Development of Tolerance
Arch Fam Med,
August 1, 1993;
2(8):
880 - 885.
[Abstract]
[PDF]
|
|
|
|
