TY - JOUR
T1 - Hydralazine does not Ameliorate Nitric Oxide Resistance in Chronic Heart Failure
AU - Chirkov, Yuliy
AU - De Sciscio, Michele
AU - Sverdlov, Aaron
AU - Leslie, Susan
AU - Sage, Peter
AU - Horowitz, John
PY - 2010/4
Y1 - 2010/4
N2 - Purpose: The A-HeFT trial demonstrated incremental survival with hydralazine/isosorbide dinitrate combination in African-American patients with chronic heart failure (CHF). It has been suggested that hydralazine might enhance nitric oxide (NO)-mediated effects of organic nitrates by decreasing superoxide (O2- ) formation, one of the factors inducing NO resistance. We evaluated whether hydralazine therapy potentiates nitrate-induced vasodilation and inhibition of platelet aggregation by ameliorating NO resistance. Methods: Patients (n=14) with NYHA class II-III CHF were studied in a randomised, double-blind, placebo-controlled, crossover study of the effects of hydralazine therapy (25 mg b.d., for 1 week) on physiological responsiveness to glyceryl trinitrate (GTN). Vascular response to GTN was assessed via applanation tonometry, as change in augmentation index (AIx) over time. Platelet responsiveness to GTN and sodium nitroprusside (SNP) was determined, as inhibition of ADP-induced platelet aggregation. O 2- release was evaluated during aggregation via lucigenin-derived chemiluminescence. Results: Platelet responsiveness to the NO donors GTN and SNP was impaired, denoting the presence of severe NO resistance. Hydralazine therapy decreased systolic blood pressure by 6.8±10.5 (S.D.) mmHg (p=0.02), and caused a reduction in AIx by 15±24% (p=0.03). However, there were no significant changes in platelet aggregability and associated O2- release, or in platelet or vascular responses to NO donor. Conclusion: The results of the present study do not support the assumption that hydralazine could be viewed as a "NO enhancer"; there is no evidence of attenuation of NO resistance by hydralazine treatment.
AB - Purpose: The A-HeFT trial demonstrated incremental survival with hydralazine/isosorbide dinitrate combination in African-American patients with chronic heart failure (CHF). It has been suggested that hydralazine might enhance nitric oxide (NO)-mediated effects of organic nitrates by decreasing superoxide (O2- ) formation, one of the factors inducing NO resistance. We evaluated whether hydralazine therapy potentiates nitrate-induced vasodilation and inhibition of platelet aggregation by ameliorating NO resistance. Methods: Patients (n=14) with NYHA class II-III CHF were studied in a randomised, double-blind, placebo-controlled, crossover study of the effects of hydralazine therapy (25 mg b.d., for 1 week) on physiological responsiveness to glyceryl trinitrate (GTN). Vascular response to GTN was assessed via applanation tonometry, as change in augmentation index (AIx) over time. Platelet responsiveness to GTN and sodium nitroprusside (SNP) was determined, as inhibition of ADP-induced platelet aggregation. O 2- release was evaluated during aggregation via lucigenin-derived chemiluminescence. Results: Platelet responsiveness to the NO donors GTN and SNP was impaired, denoting the presence of severe NO resistance. Hydralazine therapy decreased systolic blood pressure by 6.8±10.5 (S.D.) mmHg (p=0.02), and caused a reduction in AIx by 15±24% (p=0.03). However, there were no significant changes in platelet aggregability and associated O2- release, or in platelet or vascular responses to NO donor. Conclusion: The results of the present study do not support the assumption that hydralazine could be viewed as a "NO enhancer"; there is no evidence of attenuation of NO resistance by hydralazine treatment.
KW - Chronic heart failure
KW - Glyceryl trinitrate
KW - Hydralazine
KW - Nitric oxide
KW - Platelet aggregation
KW - Superoxide
KW - Vasodilatation
UR - http://www.scopus.com/inward/record.url?scp=77955416594&partnerID=8YFLogxK
U2 - 10.1007/s10557-010-6233-0
DO - 10.1007/s10557-010-6233-0
M3 - Article
SN - 0920-3206
VL - 24
SP - 131
EP - 137
JO - CARDIOVASCULAR DRUGS AND THERAPY
JF - CARDIOVASCULAR DRUGS AND THERAPY
IS - 2
ER -