Evidence of impaired hypoxic vasodilation after intermediate-duration hypoxic exposure in humans.
Systemic hemodynamics, including forearm blood flow and ventilatory parameters, were evaluated in 21 subjects before and after exposure to 8 h of poikilocapnic hypoxia. To evaluate the role of sympathetic nervous system activation in the changes, in 10 of these subjects, we measured muscle sympathetic nerve activity (MSNA) before and after exposure, and the remaining 11 subjects received intra-arterial phentolamine infusion in the brachial artery to define vascular tone in the absence of sympathetically mediated vasoconstriction. Short-term ventilatory acclimatization occurred as evidenced by a decrease in resting Pco(2) (from 42 +/- 1.4 to 37 +/- 0.96 mmHg) and by an increase in the slope of the ventilatory response to acute hypoxia [from 0.7 +/- 0.1 to 1.2 +/- 0.2 l.min(-1).%Sp(O(2)) (blood O(2) saturation from pulse oximetry)] after exposure. Subjects demonstrated a significant increase in resting heart rate (from 61 +/- 2 to 65 +/- 2 beats/min) and diastolic blood pressure (from 64.8 +/- 2.7 to 70.4 +/- 2.0 mmHg). MSNA did not change significantly after exposure, although there was a trend toward a decrease in burst frequency (from 19.8 +/- 4.1 to 14.3 +/- 1.2 bursts/min). Forearm vascular resistance showed a significant decrease after termination of exposure (from 37.7 +/- 3.6 to 27.6 +/- 2.7 mmHg.ml(-1).min.100 g tissue, P < 0.05). Initially, progressive isocapnic hypoxia elicited significant vasodilation, but after 8 h of poikilocapnic hypoxic exposure, the acute challenge failed to change forearm vascular resistance. Local alpha-blockade with phentolamine restored the vasodilatory response to acute hypoxia in the postexposure setting.
Gilmartin
Geoffrey
G
Division of Pulmonary and Critical Care and Sleep Medicine, GZ-402, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA. ggilmart@bidmc.harvard.edu
Tamisier
Renaud
R
Anand
Amit
A
Cunnington
David
D
Weiss
J Woodrow
JW
D000064:Acclimatization; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D001794:Blood Pressure; D015992:Body Mass Index; D002245:Carbon Dioxide / Q000097:blood; D005260:Female; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D010646:Phentolamine / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow; D012119:Respiration; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013997:Time Factors; D014655:Vascular Resistance; D014664:Vasodilation
D000317:Adrenergic alpha-Antagonists; D002245:Carbon Dioxide; D010646:Phentolamine