Hypercapnic vs. hypoxic control of cardiovascular, cardiovagal, and sympathetic function

We compared the integrated cardiovascular and autonomic responses to hypercapnia and hypoxia to test the hypothesis that these stimuli differentially affect muscle sympathetic nerve activity (MSNA) discharge patterns and cardiovagal and sympathetic baroreflex function in a manner related to ventilatory chemoreflex sensitivity. Six males and six females underwent 5 min of hypoxia (end-tidal Po2 = 45 Torr) and 5 min of hypercapnia (end-tidal Pco2 = +8 Torr from baseline), causing similar ventilatory responses. A downward right shift in cardiovagal set point was observed during both conditions, which was strongly related to the change in inspiratory time (Ti) from baseline to hypercapnia (r2 = 0.67, P = 0.007) and hypoxia (r2 = 0.79, P < 0.001). Cardiovagal baroreflex gain was decreased during hypoxia (20.1 +/- 6.9 vs. 8.9 +/- 5.1 ms/mmHg, P < 0.001) but not hypercapnia (26.7 +/- 12.7 vs. 23.0 +/- 9.1 ms/mmHg). Both hypoxia and hypercapnia increased MSNA burst amplitude, whereas hypoxia, but not hypercapnia, also increased in MSNA burst frequency (21 +/- 9 vs. 28 +/- 7 bursts/min, P = 0.03) and total MSNA (4.56 +/- 3.07 vs. 7.37 +/- 3.26 mV/min, P = 0.002). However, neither hypercapnia nor hypoxia affected sympathetic burst probability or baroreflex gain. Hypoxia also caused a greater reduction in total peripheral resistance (P = 0.04), a greater increase in heart rate (P = 0.002), and a trend for a greater cardiac output response (P = 0.06) compared with hypercapnia. Nonetheless, central venous pressure remained unchanged during either condition. These results suggest that hypercapnia and hypoxia exert differential effects on cardiovagal, but not sympathetic, baroreflex gain and set point in a manner not related to ventilatory chemoreflex sensitivity. Furthermore, the data suggest that the individual's respiratory pattern to hypoxia or hypercapnia, as reflected in the inspiratory time, was a strong determinant of cardiovagal baroreflex set- point rather than the total ventilatory chemoreflex gain per se.