Hypoxemia and hypercapnia synergistically mediate peripheral vasoconstriction, whereas hypercapnia mediates cerebral vasodilation in resting humans.

Simultaneous hypoxemia and hypercapnia frequently occur in conditions such as obstructive sleep apnea, which may cause peripheral and cerebral vascular dysfunction. However, how hypoxemia and hypercapnia interact in regulating peripheral and cerebral vascular responses remains incompletely understood. Eleven healthy young adults (4 females) completed three resting gas-inhalation trials (5-6 min) under different arterial O2 and CO2 conditions: 1) hypoxemic normocapnia (percutaneous arterial oxygen saturation ∼85%; Hypoxemia), 2) normoxic hypercapnia (end-tidal CO2 partial pressure ∼55 mmHg; Hypercapnia), and 3) hypoxemic hypercapnia (Combined). Femoral artery blood flow and middle cerebral artery mean blood velocity were continuously assessed using Doppler ultrasound and transcranial Doppler ultrasonography, respectively. These values were divided by mean arterial pressure measured by finger photoplethysmography to calculate leg vascular conductance and cerebrovascular conductance index (CVCi). Total vascular conductance was calculated as cardiac output (model-flow method) divided by mean arterial pressure. Relative to before gas inhalation, leg vascular conductance remained unchanged in all trials, whereas total vascular conductance increased during Hypoxemia. CVCi increased during Hypercapnia and Combined. When comparing the summed isolated responses (Hypoxemia + Hypercapnia) with the Combined, changes from baseline (Δ values) of leg vascular conductance tended to be lower (P = 0.054), and total vascular conductance was lower (P = 0.031) in Combined. By contrast, Δ CVCi did not differ between the summed isolated vs. Combined (P = 1.000). We show that hypoxemia and hypercapnia interact to augment systemic vasoconstriction, whereas hypercapnia-induced cerebral vasodilation is well preserved when combined with hypoxemia.NEW & NOTEWORTHY Combined hypoxemia and hypercapnia, which occurs in obstructive sleep apnea, tended to produce greater reductions in leg vascular conductance and a significantly greater reduction in total vascular conductance compared with the sum of the isolated effects. Cerebral vascular conductance index increased to a similar extent during the combined compared with the summed conditions. We show that hypoxemia and hypercapnia interact to augment systemic vasoconstriction, whereas hypercapnia-induced cerebral vasodilation is maintained when combined with hypoxemia.