Balance between cardiac output and sympathetic nerve activity in resting humans: role in arterial pressure regulation

Abstract

Large, reproducible interindividual differences exist in resting sympathetic nerve activity among normotensive humans with similar arterial pressures, resulting in a lack of correlation between muscle sympathetic nerve activity (MSNA) and arterial pressure among individuals. Although it is known that the arterial pressure is the main short-term determinant of MSNA in humans via the arterial baroreflex, the lack of correlation among individuals suggests that the level of arterial pressure is not the only important input in regulation of MSNA in humans. We studied the relationship between cardiac output (CO) and baroreflex control of sympathetic activity by measuring MSNA (peroneal microneurography), arterial pressure (arterial catheter), CO (acetylene uptake technique) and heart rate (HR; electrocardiogram) in 17 healthy young men during 20 min of supine rest. Across individuals, MSNA did not correlate with mean or diastolic blood pressure (r<0.01 for both), but displayed a significant negative correlation with CO (r=-0.71, P=0.001). To assess whether CO is related to arterial baroreflex control of MSNA, we constructed a baroreflex threshold diagram for each individual by plotting the percentage occurrence of a sympathetic burst against diastolic pressure. The mid-point of the diagram (T50) at which 50% of cardiac cycles are associated with bursts, was inversely related to CO (r=-0.75, P<0.001) and stroke volume (SV) (r=-0.57, P=0.015). We conclude that dynamic inputs from CO and SV are important in regulation of baroreflex control of MSNA in healthy, normotensive humans. This results in a balance between CO and sympathetically mediated vasoconstriction that may contribute importantly to normal regulation of arterial pressure in humans.

Figure 1. Regression analysis of MSNA with MAP and CO

A, lack of correlation between mean arterial pressure (MAP) and MSNA across all subjects. B, linear regression analysis showing significant inverse correlation between CO and MSNA.

Figure 2. Linear regression plot showing significant correlation between MSNA and TPR

Figure 3. Representative example of a threshold curve in one individual

Lower diastolic pressures were associated with a higher percentage occurrence of sympathetic bursts, and vice-versa. The T₅₀ value is the diastolic pressure at which 50% of cardiac cycles are associated with sympathetic bursts (in this case, 68.3 mmHg).

Figure 4. Linear regression plots of the relationships between T₅₀ and CO, SV and HR

A, linear regression plot of the relationship between T₅₀ and CO showing significant inverse correlation. B, the linear regression plot for T₅₀versus SV also shows a significant inverse correlation, suggesting that SV may contribute to the mechanism by which CO influences baroreflex control of MSNA. C, the relationship between T₅₀ and HR was weaker and non-significant, suggesting that HR may be less important with regard to the CO–baroreflex interaction.

Figure 5. Linear regression analysis of MSNA as a function of T₅₀

Baroreflex control of MSNA, as represented by the T₅₀ value, was predictive of MSNA at rest among individuals.