Hydralazine does not Ameliorate Nitric Oxide Resistance in Chronic Heart Failure
- First Online:
- 172 Downloads
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.
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. O2− release was evaluated during aggregation via lucigenin-derived chemiluminescence.
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.
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.
Key wordsChronic heart failure Glyceryl trinitrate Hydralazine Nitric oxide Platelet aggregation Superoxide Vasodilatation
- 11.Chirkov YY, De Sciscio M, Sverdlov AL, Leslie S, Horowitz JD. Is there a pharmacological hydralazine/nitrate interaction in chronic heart failure? (abstract). Eur Heart J. 2008;29:300 [P1956].Google Scholar
- 21.Kinlough-Rathbone RL, Packham MA, Mustard JF. Platelet aggregation. In: Harker LA, Zimmerman TS, editors. Measurements of platelet function. New York: Churchill Livingstone; 1983. p. 64–91.Google Scholar