Effects of regional phentolamine on hypoxic vasodilatation in healthy humans

1. Limb vascular beds exhibit a graded dilatation in response to hypoxia de spite increased sympathetic vasoconstrictor nerve activity. We investigated the extent to which sympathetic vasoconstriction can mask hypoxic vasodila tation and assessed the relative contributions of beta -adrenergic and nitr ic oxide (NO) pathways to hypoxic vasodilatation. 2. We measured forearm blood flow responses (plethysmography) to isocapnic hypoxia (arterial saturation similar to 85%) in eight healthy men and women (18-26 years) after selective alpha -adrenergic blockade (phentolamine) of one forearm. Subsequently, we measured hypoxic responses after combined al pha- and beta -adrenergic blockade (phentolamine and propranolol) and after combined alpha- and beta -adrenergic blockade coupled with NO synthase inh ibition (N-G-monomethyl-L-arginine, L-NMMA). 3. Hypoxia increased forearm vascular conductance by 49.0 +/- 13.5% after p hentolamine (compared to +16.8 +/- 7.0% in the control arm without phentola mine, P < 0.05). After addition of propranolol, the forearm vascular conduc tance response to hypoxia was reduced by -50%, but dilatation was still pre sent (+24.7 +/- 7.0 %, P < 0.05 vs. normoxia). NT hen L-NMMA was added, the re 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 <alpha>-adrenergic blockade unmasked a greater hypoxic vasodilatation than occurs in the presence of functional Sympatheti c nervous system responses to hypoxia. Furthermore, approximately half of t he hypoxic vasodilatation in the forearm appears to be mediated by beta -ad renergic receptor-mediated pathways. Finally, since considerable dilatation persists in the presence of both beta -adrenergic blockade and NO synthase inhibition, it is likely that an additional vasodilator mechanism is activ ated by hypoxia in humans.