Hypoxic modulation of exogenous nitrite-induced vasodilation in humans

Abdul R. Maher, Alexandra B. Milsom, Prasad Gunaruwan, Khalid Abozguia, Ibrar Ahmed, Rebekah A. Weaver, Philip Thomas, Houman Ashrafian, Gustav V. R. Born, Philip E. James, Michael Frenneaux

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Abstract

Background— It has been proposed that under hypoxic conditions, nitrite may release nitric oxide, which causes potent vasodilation. We hypothesized that nitrite would have a greater dilator effect in capacitance than in resistance vessels because of lower oxygen tension and that resistance-vessel dilation should become more pronounced during hypoxemia. The effect of intra-arterial infusion of nitrite on forearm blood flow and forearm venous volumes was assessed during normoxia and hypoxia.

Methods and Results— Forty healthy volunteers were studied. After baseline infusion of 0.9% saline, sodium nitrite was infused at incremental doses from 40 nmol/min to 7.84 µmol/min. At each stage, forearm blood flow was measured by strain-gauge plethysmography. Forearm venous volume was assessed by radionuclide plethysmography. Changes in forearm blood flow and forearm venous volume in the infused arm were corrected for those in the control arm. The peak percentage of venodilation during normoxia was 35.8±3.4% (mean±SEM) at 7.84 µmol/min (P<0.001) and was similar during hypoxia. In normoxia, arterial blood flow, assessed by the forearm blood flow ratio, increased from 1.04±0.09 (baseline) to 1.62±0.18 (nitrite; P<0.05) versus 1.07±0.09 (baseline) to 2.37±0.15 (nitrite; P<0.005) during hypoxia. This result was recapitulated in vitro in vascular rings.

Conclusions— Nitrite is a potent venodilator in normoxia and hypoxia. Arteries are modestly affected in normoxia but potently dilated in hypoxia, which suggests the important phenomenon of hypoxic augmentation of nitrite-mediated vasodilation in vivo. The use of nitrite as a selective arterial vasodilator in ischemic territories and as a potent venodilator in heart failure has therapeutic implications.
Original languageEnglish
Pages (from-to)670-677
Number of pages8
JournalCirculation
Volume117
Issue number5
Early online date22 Jan 2008
DOIs
Publication statusPublished - 5 Feb 2008

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Nitrites
Vasodilation
Forearm
Plethysmography
Arm
Sodium Nitrite
Intra Arterial Infusions
Vasodilator Agents
Radioisotopes
Blood Vessels
Hypoxia
Dilatation
Healthy Volunteers
Nitric Oxide
Heart Failure
Arteries
Oxygen

Keywords

  • nitrite
  • vascular function

Cite this

Maher, A. R., Milsom, A. B., Gunaruwan, P., Abozguia, K., Ahmed, I., Weaver, R. A., ... Frenneaux, M. (2008). Hypoxic modulation of exogenous nitrite-induced vasodilation in humans. Circulation, 117(5), 670-677. https://doi.org/10.1161/CIRCULATIONAHA.107.188519

Hypoxic modulation of exogenous nitrite-induced vasodilation in humans. / Maher, Abdul R.; Milsom, Alexandra B.; Gunaruwan, Prasad; Abozguia, Khalid; Ahmed, Ibrar; Weaver, Rebekah A.; Thomas, Philip; Ashrafian, Houman; Born, Gustav V. R.; James, Philip E.; Frenneaux, Michael.

In: Circulation, Vol. 117, No. 5, 05.02.2008, p. 670-677.

Research output: Contribution to journalArticle

Maher, AR, Milsom, AB, Gunaruwan, P, Abozguia, K, Ahmed, I, Weaver, RA, Thomas, P, Ashrafian, H, Born, GVR, James, PE & Frenneaux, M 2008, 'Hypoxic modulation of exogenous nitrite-induced vasodilation in humans' Circulation, vol. 117, no. 5, pp. 670-677. https://doi.org/10.1161/CIRCULATIONAHA.107.188519
Maher AR, Milsom AB, Gunaruwan P, Abozguia K, Ahmed I, Weaver RA et al. Hypoxic modulation of exogenous nitrite-induced vasodilation in humans. Circulation. 2008 Feb 5;117(5):670-677. https://doi.org/10.1161/CIRCULATIONAHA.107.188519
Maher, Abdul R. ; Milsom, Alexandra B. ; Gunaruwan, Prasad ; Abozguia, Khalid ; Ahmed, Ibrar ; Weaver, Rebekah A. ; Thomas, Philip ; Ashrafian, Houman ; Born, Gustav V. R. ; James, Philip E. ; Frenneaux, Michael. / Hypoxic modulation of exogenous nitrite-induced vasodilation in humans. In: Circulation. 2008 ; Vol. 117, No. 5. pp. 670-677.
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T1 - Hypoxic modulation of exogenous nitrite-induced vasodilation in humans

AU - Maher, Abdul R.

AU - Milsom, Alexandra B.

AU - Gunaruwan, Prasad

AU - Abozguia, Khalid

AU - Ahmed, Ibrar

AU - Weaver, Rebekah A.

AU - Thomas, Philip

AU - Ashrafian, Houman

AU - Born, Gustav V. R.

AU - James, Philip E.

AU - Frenneaux, Michael

PY - 2008/2/5

Y1 - 2008/2/5

N2 - Background— It has been proposed that under hypoxic conditions, nitrite may release nitric oxide, which causes potent vasodilation. We hypothesized that nitrite would have a greater dilator effect in capacitance than in resistance vessels because of lower oxygen tension and that resistance-vessel dilation should become more pronounced during hypoxemia. The effect of intra-arterial infusion of nitrite on forearm blood flow and forearm venous volumes was assessed during normoxia and hypoxia.Methods and Results— Forty healthy volunteers were studied. After baseline infusion of 0.9% saline, sodium nitrite was infused at incremental doses from 40 nmol/min to 7.84 µmol/min. At each stage, forearm blood flow was measured by strain-gauge plethysmography. Forearm venous volume was assessed by radionuclide plethysmography. Changes in forearm blood flow and forearm venous volume in the infused arm were corrected for those in the control arm. The peak percentage of venodilation during normoxia was 35.8±3.4% (mean±SEM) at 7.84 µmol/min (P<0.001) and was similar during hypoxia. In normoxia, arterial blood flow, assessed by the forearm blood flow ratio, increased from 1.04±0.09 (baseline) to 1.62±0.18 (nitrite; P<0.05) versus 1.07±0.09 (baseline) to 2.37±0.15 (nitrite; P<0.005) during hypoxia. This result was recapitulated in vitro in vascular rings.Conclusions— Nitrite is a potent venodilator in normoxia and hypoxia. Arteries are modestly affected in normoxia but potently dilated in hypoxia, which suggests the important phenomenon of hypoxic augmentation of nitrite-mediated vasodilation in vivo. The use of nitrite as a selective arterial vasodilator in ischemic territories and as a potent venodilator in heart failure has therapeutic implications.

AB - Background— It has been proposed that under hypoxic conditions, nitrite may release nitric oxide, which causes potent vasodilation. We hypothesized that nitrite would have a greater dilator effect in capacitance than in resistance vessels because of lower oxygen tension and that resistance-vessel dilation should become more pronounced during hypoxemia. The effect of intra-arterial infusion of nitrite on forearm blood flow and forearm venous volumes was assessed during normoxia and hypoxia.Methods and Results— Forty healthy volunteers were studied. After baseline infusion of 0.9% saline, sodium nitrite was infused at incremental doses from 40 nmol/min to 7.84 µmol/min. At each stage, forearm blood flow was measured by strain-gauge plethysmography. Forearm venous volume was assessed by radionuclide plethysmography. Changes in forearm blood flow and forearm venous volume in the infused arm were corrected for those in the control arm. The peak percentage of venodilation during normoxia was 35.8±3.4% (mean±SEM) at 7.84 µmol/min (P<0.001) and was similar during hypoxia. In normoxia, arterial blood flow, assessed by the forearm blood flow ratio, increased from 1.04±0.09 (baseline) to 1.62±0.18 (nitrite; P<0.05) versus 1.07±0.09 (baseline) to 2.37±0.15 (nitrite; P<0.005) during hypoxia. This result was recapitulated in vitro in vascular rings.Conclusions— Nitrite is a potent venodilator in normoxia and hypoxia. Arteries are modestly affected in normoxia but potently dilated in hypoxia, which suggests the important phenomenon of hypoxic augmentation of nitrite-mediated vasodilation in vivo. The use of nitrite as a selective arterial vasodilator in ischemic territories and as a potent venodilator in heart failure has therapeutic implications.

KW - nitrite

KW - vascular function

U2 - 10.1161/CIRCULATIONAHA.107.188519

DO - 10.1161/CIRCULATIONAHA.107.188519

M3 - Article

VL - 117

SP - 670

EP - 677

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 5

ER -