Effects of regional phentolamine on hypoxic vasodilatation in healthy humans.
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 beta-adrenergic and nitric oxide (NO) pathways to hypoxic vasodilatation. 2. We measured forearm blood flow responses (plethysmography) to isocapnic hypoxia (arterial saturation approximately 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 alpha- and beta-adrenergic blockade (phentolamine and propranolol) and after combined alpha- and beta-adrenergic blockade coupled with NO synthase inhibition (N(G)-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 approximately 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 alpha-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 beta-adrenergic 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 activated by hypoxia in humans.
Weisbrod
C J
CJ
Department of Anesthesiology and General Clinical Research Center, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Minson
C T
CT
Joyner
M J
MJ
Halliwill
J R
JR
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D001158:Arteries; D001794:Blood Pressure; D002395:Catecholamines / Q000097:blood; D005260:Female; D005542:Forearm / Q000098:blood supply; D005740:Gases / Q000097:blood; D006339:Heart Rate; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012119:Respiration; D012867:Skin / Q000098:blood supply; D014664:Vasodilation / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D005740:Gases; D011433:Propranolol; D010646:Phentolamine