Influence of caffeine on hypercapnic pressor and heart rate responses in healthy men and women

Introduction: Hypercapnia-mediated chemoreceptor activation elicits sympathoexcitation, which can increase blood pressure and heart rate. Caffeine is also sympathoexcitatory, but it is unknown whether caffeine alters the hypercapnic pressor or heart rate responses. Purpose: To evaluate the impact of caffeine on hypercapnic pressor and heart rate responses in healthy men and women. Methods: Twenty-three individuals (age: 28±7 yr; body mass: 71±10 kg; height: 170±9 cm; 12 women) completed randomized, double-blind crossover trials involving caffeine (400mg) or placebo supplementation. Trials were separated by a minimum of 48 hours. Blood samples were taken 45 minutes following treatment and analyzed for plasma caffeine concentration. Sixty minutes after treatment, participants completed graded carbon dioxide (CO 2 ) exposure trials involving 5 sequential 12-minute stages breathing 0%, 2%, 4%, 6%, and 8% inspired CO 2 , all with 21% oxygen. Seven minutes into each stage, heart rate was measured using a chest-worn telemetric sensor and systolic (SBP) and diastolic (DBP) blood pressures were measured using an automated arm cuff. End-tidal CO 2 was measured using infrared capnography. We used linear mixed models to determine the main effects of inspired CO 2 and treatment (caffeine vs. placebo) on blood pressure and heart rate, as well as inspired CO 2 x treatment interactions. Paired t-tests were used to compare hypercapnic pressor and heart rate responses (the slope of blood pressure or heart rate vs. end-tidal CO 2 ) and plasma caffeine concentrations between the caffeine and placebo trials. Results: As expected, caffeine treatment increased plasma caffeine concentration compared to placebo (9.36 ± 3.52 vs. 0.65 ± 0.65 ug·mL -1 ; p<0.001). For SBP and DBP, we observed main effects of inspired CO 2 and treatment (p≤0.005), but no significant inspired CO 2 x treatment interactions. Caffeine did not significantly affect the hypercapnic pressor response for SBP (Placebo: 1.30±0.49; Caffeine: 1.05±0.48 mmHg mmHg -1 ; p=0.21) or DBP (Placebo: 0.87±0.38; Caffeine: 0.65±0.34 mmHg mmHg -1 ; p=0.06). For heart rate, we observed a main effect of inspired CO 2 (p<0.001), but no significant effect of treatment or inspired CO 2 x treatment interaction. The hypercapnic heart rate response was not significantly altered by caffeine (Placebo: 0.96±0.50; Caffeine: 0.80±0.43 beats min -1 mmHg -1 ; p=0.23). Conclusion: Our novel findings indicate that caffeine does not alter the hypercapnic pressor or heart rate responses in healthy humans. In support of previous literature, we found that hypercapnia and caffeine both augment blood pressure and that hypercapnia, but not caffeine, increases heart rate. Funded by USAMRDC: author views not representative of the U.S. Army or DoD. Funded by USAMRDC: author views not representative of the U.S. Army or DoD. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.