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Intra-arterial inorganic nitrite preferentially dilates the capacitance bed in chronic heart failure
  1. AR Maher,
  2. S Arif,
  3. J Ormerod,
  4. M Nasimizadeh,
  5. I Ahmed,
  6. M Frenneaux
  1. Birmingham University, Birmingham, UK

Abstract

Background The potential role of inorganic nitrite in mediating vasodilation continues to attract a great deal of attention. This has led to therapeutic avenues being investigated. Chronic heart failure (CHF) is a condition that lends itself well to such investigation as the release of nitric oxide (NO) from nitrite appears to be dependent on the ambient oxygen tension. Accordingly, nitrite could represent a venodilator, which under arterial normoxia only modestly relaxes arteries potentially reducing central filling pressures in heart failure while avoiding hypotension. However, the low output state that characterises CHF may mitigate some of this venoselectivity. To address this concern, in anticipation of the use of nitrite pharmacologically, the effect of a local intrabrachial infusion of sodium nitrite on vascular function was studied.

Methods 18 patients with CHF were studied and the results compared with 15 healthy controls. Following baseline infusion of 0.9% saline, sodium nitrite was infused at incremental doses from 314 nmol/minute to 7.84 μmol/minute. At each stage, forearm blood flow (FBF) was measured using strain gauge plethysmography, was corrected for changes in the control arm and was thereby expressed as the FBF ratio. Forearm venous volume (FVV) was assessed by radionuclide plethysmography. FVV in the infused arm was similarly corrected for changes in the control arm.

Results A statistically significant venodilation observed at peak nitrite dose in CHF subjects (24.3% ± 7.9) (mean ± SEM) at 7.84 μmol/minute (p = 0.02) was not significantly different to controls (26.8 ± 4.6). Importantly, the nitrite concentration–response curves were similar, suggesting the absence of nitrite tolerance in CHF. Arterial blood flow, assessed by the FBF ratio, increased from 1.15 ± 0.07 (baseline) to 1.49 ± 0.26 (nitrite) but was statistically no different to the response in the control group 1.62 ± 0.13; p = NS).

Conclusions In patients with CHF vascular responses to nitrite are similar to those seen in healthy controls, demonstrating relative “veno-selectivity”. This reassuring observation provides a clear rationale to investigate an adjunctive therapeutic role for nitrite in heart failure. The use of such an “unbalanced” vasodilator would offer distinct advantages as it would reduce elevated filling pressures while avoiding the deleterious effects of arterial vasodilation, a characteristic that would be particularly beneficial in the presence of diastolic ventricular interaction.

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