Group-Averaged Data for Cardiovascular and Neural Variables in Men and Women
shows average values for resting arterial pressures, heart rate, heart rate variability, cardiac output, and TPR in young and older men. Although resting heart rate was not different between groups, heart rate variability was lower in the older men compared with the younger men (P<0.05). There was a large variability in cardiac output, particularly among the older subjects. Two of the older subjects exhibited a very large cardiac output and stroke volume (see circled data points in ); when these were removed from the analysis, average cardiac output in the older men was 5.8±0.3 L/min−1. MSNA was greater in the older men compared with the younger men, both when expressed as burst frequency and as burst incidence. Furthermore, venous plasma norepinephrine was greater in the older men compared with the younger men.
Cardiovascular and Neural Variables in Young (n=14) and Older Men (n=17)
Figure 3 Regression analysis of MSNA with cardiac output in young (n=14) and older men (n=17). The inverse relationship between MSNA and cardiac output in young men was not observed in older men (r=0.13; P>0.05). This lack of relationship persisted when (more ...)
Interindividual Relationships Between Neural and Hemodynamic Variables in Young and Older Men
Relationships between MSNA and cardiovascular variables are demonstrated in through , with MSNA expressed as burst incidence (bursts per 100 heartbeats). The relationships between MSNA expressed as bursts frequency (bursts per minute) and hemodynamic variables showed similar trends and are reported in the text.
Relationship of MSNA with DBP in young (n=14) and old men (n=17). There was no relationship of DBP with MSNA in the young men, but a positive relationship existed in the older men.
Figure 5 Regression analysis of MSNA with (A) change in FBF and (B) percentage change in FBF after intra-arterial infusion of norepinephrine (4 ng [100 mL−1]/min−1) in young (n=14; left) and older (n=16; right) men. The relationship between MSNA (more ...)
In young men, there was no relationship between MSNA and DBP when MSNA was expressed as burst incidence () and burst frequency (r=−0.17), whereas in older men there was a positive correlation, which showed a strong trend for significance (burst incidence: P=0.05; ; burst frequency: r=0.47). As reported previously, there was a positive relationship between MSNA and TPR in the younger men (burst incidence: r=0.51; burst frequency: r=0.51; P<0.05). However, there was no relationship between MSNA and TPR in the older men (burst incidence: r=−0.06; burst frequency: r=−0.10; P>0.05). shows the relationship between MSNA and cardiac output in the young and older groups. As reported previously, MSNA was inversely correlated with cardiac output in the younger men (burst frequency: r=−0.64; P<0.05). Conversely, MSNA was unrelated to cardiac output in the older men (burst frequency: r=0.13; P<0.05). Because of the large variability seen in the cardiac output values in the older men, we also performed the analysis after removing the 2 subjects with the highest values (circled data in ) and found no significant relationship between cardiac output and MSNA (burst incidence: r=0.29, P=0.3; burst frequency: r=0.35, P=0.2). Furthermore, there was no correlation between heart rate and MSNA in the younger (burst incidence: r=−0.23; burst frequency: r=0.32; P>0.05) and older men (burst incidence: r=−0.24; burst frequency: r=0.20; P>0.05). Additionally, there was no correlation of MSNA with heart rate variability in the younger (burst incidence: r=0.30; burst frequency: r=−0.03; P>0.05) and = older men (burst incidence: r=−0.15; burst frequency: r=−0.25; P>0.05).
FBF Responses to α-Adrenergic Agonists
Because of problems with recording equipment, we excluded 1 older man from the FBF analyses. On average, resting FBF before norepinephrine and tyramine infusions was slightly higher in the older men (n=16) compared with the younger men (n=14), although the difference between groups was not significant (norepinephrine baseline, , P=0.3; tyramine baseline, 2.7±0.5 versus 2.4±0.1 mL (100 mL)−1/min−1, P=0.2). Therefore, we chose to express changes in FBF to drug infusions as a percentage change from baseline. Norepinephrine and tyramine caused dose-dependent reductions in FBF in all of the participants. Average percentage changes in FBF to norepinephrine were smaller in the older compared with the younger men (norepinephrine 2: −26±3% [older] versus −33±7% (younger); norepinephrine 4: −36±5% [older] versus −42±6% [older]; norepinephrine 8: −49±5% [older] versus −56±5% [younger]; PANOVA=0.04). Average percentage changes in FBF to tyramine were significantly smaller in the older men compared with the younger men (tyramine 3: −13±4% [older] versus 27±5% [younger]; tyramine 6: 36±5% [older] versus 43±5% [younger]; tyramine 12: 48±6% [older] versus 53±5% [younger]; PANOVA=0.04).
To address the potential for differences in norepinephrine release with tyramine among subjects, we measured the arteriovenous (a-v) difference in plasma norepinephrine during tyramine infusion in both groups. The a-v difference is reported as the absolute value of the difference, because our goal was to use this as an index of the amount of norepinephrine that the blood vessels were exposed to (ie, a positive value). Because of the vasoconstriction caused by tyramine infusion, we could not obtain venous blood from all of the participants; therefore, we were able to compare a-v differences of 12 older men with those of 10 younger men. Tyramine induced significant increases in the a-v difference of norepinephrine in both groups; however, the a-v difference was not different between the older men and younger men at all of the doses (tyramine 3: 92±21 pg/mL−1 [older] versus 50±12 pg/mL−1 [younger]; tyramine 6: 256±39 pg/mL−1 versus 243±38 pg/mL−1; tyramine 12: 550±110 pg/mL−1 versus 668±97 pg/mL−1).
shows changes in FBF plotted against the a-v difference of norepinephrine during tyramine infusion. Changes in FBF in response to tyramine infusion were not different between the 2 groups of men when expressed as absolute changes (PANOVA>0.5). However, when changes were expressed as a percentage of the baseline flow, the older men had a significantly smaller change in FBF at all of the levels of tyramine infusion (PANOVA<0.05).
Figure 4 Vasoconstrictor responses to tyramine (TYR) as a function of the a-v difference in norepinephrine (NE) in young (n=10) and older (n=12) men. Changes in FBF expressed in absolute numbers (left) and percentage (right). The older men exhibited a blunted (more ...)
MSNA and FBF Responses to α-Adrenergic Stimulation
In young men, as reported previously, the change in FBF to norepinephrine was positively related to MSNA. This is shown for burst incidence for the middle dose of norepinephrine (4 ng [100 mL−1]/min−1) in (for burst frequency; r=0.63; P<0.05), such that individuals with high MSNA showed less vasoconstriction to a given dose of norepinephrine and vice versa. This relationship was not observed in the older men in the present study (burst incidence; ; burst frequency: r=−0.19; P>0.05).
Similarly, in young men, the change in FBF to tyramine was positively related to MSNA. For example, for the middle dose of tyramine (6 μg [100 mL−1]/min−1), individuals with a high MNSA exhibited a lower vasoconstriction, and those with lower MSNA has a higher vasoconstrictor response (burst incidence: r=0.56; burst frequency: r=0.62; P< 0.05). In older men, there was no relationship between MSNA and the decrease in FBF during tyramine (burst incidence: r=−0.19; burst frequency: r=−0.04).