Noradrenergic vascular hyper-responsiveness in human hpertension is dependent on oxygen free radical impairment of nitric oxide activity

Giuseppe Lembo, Carmine Vecchione, Raffaele Izzo, Luigi Fratta, Dario Fontana, Gennaro Marino, Giovanni Pilato, Bruno Trimarco

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background - Noradrenergic vascular hyper-responsiveness is a hallmark of essential hypertension. To evaluate whether nitric oxide plays a role in the enhanced vascular response to norepinephrine in hypertension, we examined 32 hypertensives and 28 normotensives who were distributed in 3 experimental series. Methods and Results - In the first series, we measured the forearm blood flow (FBF) response to a norepinephrine infusion under control conditions and during the infusion of L-N-monomethylarginine (L-NMMA). Norepinephrine evoked dose-dependent vasoconstriction that was greater in hypertensives than in normotensives (maximum FBF, -61 ± 1 versus -51 ± 1%; P <0.01). During L-NMMA infusion, norepinephrine vasoconstriction was not modified in hypertensives; however, it was potentiated in normotensives (maximum FBF, -64 ± 2%; P <0.01). In the second series, we tested whether norepinephrine vasoconstriction could be affected by an antioxidant such as ascorbic acid. Norepinephrine vasoconstriction was blunted by ascorbic acid administration only in hypertensives (maximum FBF, -49 ± 3 versus -63 ± 2%; P <0.01); the vasoconstriction became similar to that observed in normotensives. During ascorbic acid plus L-NMMA administration, the vascular response to norepinephrine increased to a similar extent in both study groups. To rule out the possibility that the effect of ascorbic acid on norepinephrine vasoconstriction could depend on adrenergic receptor-induced nitric oxide release, in the last series we inhibited endogenous nitric oxide and replaced it with an exogenous nitric oxide donor (sodium nitroprusside). Even in these conditions, ascorbic acid attenuated norepinephrine vasoconstriction only in hypertensives (maximum FBF, -50 ± 2 versus -62 ± 1%; P <0.01). Conclusions - Our data demonstrate that noradrenergic vascular hyper-responsiveness in hypertension is dependent on an impairment of nitric oxide activity that is realized through norepinephrine-induced oxygen free radical production.

Original languageEnglish
Pages (from-to)552-557
Number of pages6
JournalCirculation
Volume102
Issue number5
Publication statusPublished - Aug 1 2000

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Free Radicals
Blood Vessels
Reactive Oxygen Species
Norepinephrine
Nitric Oxide
Vasoconstriction
Forearm
Ascorbic Acid
Hypertension
Nitric Oxide Donors
Nitroprusside
Adrenergic Receptors
Antioxidants

Keywords

  • Antioxidants
  • Blood flow
  • Endothelium
  • Hypertension
  • Norepinephrine

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Noradrenergic vascular hyper-responsiveness in human hpertension is dependent on oxygen free radical impairment of nitric oxide activity. / Lembo, Giuseppe; Vecchione, Carmine; Izzo, Raffaele; Fratta, Luigi; Fontana, Dario; Marino, Gennaro; Pilato, Giovanni; Trimarco, Bruno.

In: Circulation, Vol. 102, No. 5, 01.08.2000, p. 552-557.

Research output: Contribution to journalArticle

Lembo, Giuseppe ; Vecchione, Carmine ; Izzo, Raffaele ; Fratta, Luigi ; Fontana, Dario ; Marino, Gennaro ; Pilato, Giovanni ; Trimarco, Bruno. / Noradrenergic vascular hyper-responsiveness in human hpertension is dependent on oxygen free radical impairment of nitric oxide activity. In: Circulation. 2000 ; Vol. 102, No. 5. pp. 552-557.
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T1 - Noradrenergic vascular hyper-responsiveness in human hpertension is dependent on oxygen free radical impairment of nitric oxide activity

AU - Lembo, Giuseppe

AU - Vecchione, Carmine

AU - Izzo, Raffaele

AU - Fratta, Luigi

AU - Fontana, Dario

AU - Marino, Gennaro

AU - Pilato, Giovanni

AU - Trimarco, Bruno

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N2 - Background - Noradrenergic vascular hyper-responsiveness is a hallmark of essential hypertension. To evaluate whether nitric oxide plays a role in the enhanced vascular response to norepinephrine in hypertension, we examined 32 hypertensives and 28 normotensives who were distributed in 3 experimental series. Methods and Results - In the first series, we measured the forearm blood flow (FBF) response to a norepinephrine infusion under control conditions and during the infusion of L-N-monomethylarginine (L-NMMA). Norepinephrine evoked dose-dependent vasoconstriction that was greater in hypertensives than in normotensives (maximum FBF, -61 ± 1 versus -51 ± 1%; P <0.01). During L-NMMA infusion, norepinephrine vasoconstriction was not modified in hypertensives; however, it was potentiated in normotensives (maximum FBF, -64 ± 2%; P <0.01). In the second series, we tested whether norepinephrine vasoconstriction could be affected by an antioxidant such as ascorbic acid. Norepinephrine vasoconstriction was blunted by ascorbic acid administration only in hypertensives (maximum FBF, -49 ± 3 versus -63 ± 2%; P <0.01); the vasoconstriction became similar to that observed in normotensives. During ascorbic acid plus L-NMMA administration, the vascular response to norepinephrine increased to a similar extent in both study groups. To rule out the possibility that the effect of ascorbic acid on norepinephrine vasoconstriction could depend on adrenergic receptor-induced nitric oxide release, in the last series we inhibited endogenous nitric oxide and replaced it with an exogenous nitric oxide donor (sodium nitroprusside). Even in these conditions, ascorbic acid attenuated norepinephrine vasoconstriction only in hypertensives (maximum FBF, -50 ± 2 versus -62 ± 1%; P <0.01). Conclusions - Our data demonstrate that noradrenergic vascular hyper-responsiveness in hypertension is dependent on an impairment of nitric oxide activity that is realized through norepinephrine-induced oxygen free radical production.

AB - Background - Noradrenergic vascular hyper-responsiveness is a hallmark of essential hypertension. To evaluate whether nitric oxide plays a role in the enhanced vascular response to norepinephrine in hypertension, we examined 32 hypertensives and 28 normotensives who were distributed in 3 experimental series. Methods and Results - In the first series, we measured the forearm blood flow (FBF) response to a norepinephrine infusion under control conditions and during the infusion of L-N-monomethylarginine (L-NMMA). Norepinephrine evoked dose-dependent vasoconstriction that was greater in hypertensives than in normotensives (maximum FBF, -61 ± 1 versus -51 ± 1%; P <0.01). During L-NMMA infusion, norepinephrine vasoconstriction was not modified in hypertensives; however, it was potentiated in normotensives (maximum FBF, -64 ± 2%; P <0.01). In the second series, we tested whether norepinephrine vasoconstriction could be affected by an antioxidant such as ascorbic acid. Norepinephrine vasoconstriction was blunted by ascorbic acid administration only in hypertensives (maximum FBF, -49 ± 3 versus -63 ± 2%; P <0.01); the vasoconstriction became similar to that observed in normotensives. During ascorbic acid plus L-NMMA administration, the vascular response to norepinephrine increased to a similar extent in both study groups. To rule out the possibility that the effect of ascorbic acid on norepinephrine vasoconstriction could depend on adrenergic receptor-induced nitric oxide release, in the last series we inhibited endogenous nitric oxide and replaced it with an exogenous nitric oxide donor (sodium nitroprusside). Even in these conditions, ascorbic acid attenuated norepinephrine vasoconstriction only in hypertensives (maximum FBF, -50 ± 2 versus -62 ± 1%; P <0.01). Conclusions - Our data demonstrate that noradrenergic vascular hyper-responsiveness in hypertension is dependent on an impairment of nitric oxide activity that is realized through norepinephrine-induced oxygen free radical production.

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KW - Blood flow

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