Dopamine Impairs Baroreflex Mediated Sympathetic Arterial Pressure Regulation While Maintaining Arterial Pressure in Rats

Dopamine is commonly used for treating hemodynamic collapse. However, recent clinical trials have reported that dopamine administration does not necessarily lead to improved patient outcomes, and the underlying reasons remain unclear. Among the mechanisms of autonomic cardiovascular regulation, the arterial baroreflex is one of the most important negative feedback systems for maintaining and stabilizing arterial pressure (AP). The impact of dopamine on baroreflex-mediated sympathetic AP regulation has not been clarified. To test the hypothesis that dopamine affects baroreflex-mediated sympathetic AP regulation, we examined the effects of various doses of dopamine on AP regulation using a baroreflex open-loop analysis. Male Wistar–Kyoto rats were used (n = 8, 14.0 ± 0.6 weeks of age, 367 ± 21 g, mean ± SD). We measured sympathetic nerve activity (SNA) and AP in response to stepwise changes in carotid sinus pressure (CSP), before and during intravenous administration of low-, medium-, and high-dose dopamine (2, 10, and 20 µg·kg −1 ·min −1 , respectively), in anesthetized rats. We analyzed the CSP-SNA relationship (neural arc) and the SNA-AP relationship (peripheral arc) and constructed an equilibrium diagram. The gain at the operating point was calculated from the product of the tangential slope of the neural arc and the slope of the peripheral arc. High-dose dopamine significantly reduced the maximum gain [from 1.898 ± 0.150 to 1.277 ± 0.205 ( P = 0.014) in %/mmHg] and increased the lower limit [from 34.12 ± 6.03 to 56.84 ± 12.40 ( P = 0.017) in %] of the neural arc. Medium- and high-dose dopamine significantly reduced the slope of the peripheral arc [from 0.806 ± 0.079 to 0.645 ± 0.091 ( P = 0.031) and 0.633 ± 0.100 ( P = 0.020) in mmHg/%] and the operating-point gain [from 0.800 ± 0.187 to 0.462 ± 0.153 ( P = 0.008) and 0.345 ± 0.122 ( P < 0.001) in mmHg/mmHg] compared to baseline, while maintaining the operating-point AP [from 94.5 ± 2.9 to 87.8 ± 4.1 (not significant) and 87.7 ± 4.5 (not significant) in mmHg]. In conclusion, medium- and high-dose dopamine maintained the operating-point AP but significantly reduced the operating-point gain for the AP regulation, potentially increasing AP variability and instability. These results may help understand why the use of dopamine did not yield favorable outcomes in past clinical trials, particularly in patients with shock where acute hemodynamic fluctuations can be life-threatening. This work was supported by the Grant-in-Aid for Scientific Research (24K23423) and the research grant from NTT Research, Inc. 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.