Effects of regional phentolamine on hypoxic vasodilation in healthy humans

Cara J. Weisbrod, Christopher T. Minson, Michael J. Joyner, John R. Halliwill

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96 Scopus citations

Abstract

1. Limb vascular beds exhibit a graded dilatation in response to hypoxia despite increased sympathetic vasoconstrictor nerve activity. We investigated the extent to which sympathetic vasoconstriction can mask hypoxic vasodilatation and assessed the relative contributions of β-adrenergic and nitric oxide (NO) pathways to hypoxic vasodilatation. 2. We measured forearm blood flow responses (plethysmography) to isocapnic hypoxia (arterial saturation ∼85%) in eight healthy men and women (18-26 years) after selective α-adrenergic blockade (phentolamine) of one forearm. Subsequently, we measured hypoxic responses after combined α- and β-adrenergic blockade (phentolamine and propranolol) and after combined α- and β-adrenergic blockade coupled with NO synthase inhibition (NG-monomethyl-L-arginine, L-NMMA). 3. Hypoxia increased forearm vascular conductance by 49.0 ± 13.5% after phentolamine (compared to +16.8 ± 7.0% in the control arm without phentolamine, P < 0.05). After addition of propranolol, the forearm vascular conductance response to hypoxia was reduced by ∼50%, but dilatation was still present (+24.7 ± 7.0%, P < 0.05 vs. normoxia). When L-NMMA was added, there was no further reduction in the forearm vascular conductance response to hypoxia (+28.2 ± 4.0%, P < 0.05 vs. normoxia). 4. Thus, selective regional α-adrenergic blockade unmasked a greater hypoxic vasodilatation than occurs in the presence of functional sympathetic nervous system responses to hypoxia. Furthermore, approximately half of the hypoxic vasodilatation in the forearm appears to be mediated by β-adrenergic receptor-mediated pathways. Finally, since considerable dilatation persists in the presence of both β-adrenergic blockade and NO synthase inhibition, it is likely that an additional vasodilator mechanism is activated by hypoxia in humans.

Original languageEnglish (US)
Pages (from-to)613-621
Number of pages9
JournalJournal of Physiology
Volume537
Issue number2
DOIs
StatePublished - Dec 1 2001

ASJC Scopus subject areas

  • Physiology

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