Joyner, Michael J.

The influence of the ovarian cycle on muscle sympathetic nerve activity (MSNA) remains controversial. Some studies report an increase of resting MSNA during the mid luteal (ML) phase of the ovarian cycle compared with the early follicular phase, whereas other studies do not. These inconsistent findings may be attributable, in part, to the variable surges in estradiol and progesterone. We tested the hypothesis that the degree of sympathoexcitation during the ML phase (ΔMSNA) is associated with changes in estradiol (ΔE 2 ) and progesterone (ΔP). Multiple regression analysis of data from previous studies with complete recordings of mean arterial pressure, MSNA, E 2 , and P during both early follicular and ML phases were available from 30 eumenorrheic women (age, 28±1 years; body mass index, 23±0 kg/m 2 ). ML phase increased E 2 (37±2 to 117±9 pg/mL; P <0.001), P (1±0 to 11±1 ng/mL; P <0.001), and MSNA (12±1 to 15±1 bursts/min; P =0.02), but did not alter mean arterial pressure (83±2 to 83±2 mm Hg; P =0.91). ΔMSNA was correlated with ΔE 2 ( r =−0.50, P =0.003) and ΔE 2 /ΔP ( r =−0.52, P =0.002) but not ΔP ( r =0.21, P =0.13). There was no association between Δmean arterial pressure and ΔE 2 ( r =−0.13, P =0.49), ΔP ( r =−0.04, P =0.83), or ΔE 2 /ΔP ( r <0.01, P =0.98). In conclusion, sympathoexcitation during the ML phase of the ovarian cycle seems to be dependent, in part, on the degree of sex steroid surges. This dynamic interaction among E 2 , P, and MSNA likely explains previously reported inconsistencies in the field; it remains possible that other sex steroids, such as testosterone, might explain further variance.

Large increases in systemic oxygen content cause substantial reductions in exercising forearm blood flow (FBF) due to increased vascular resistance. We hypothesized that 1) functional sympatholysis (blunting of sympathetic α-adrenergic vasoconstriction) would be attenuated during hyperoxic exercise and 2) α-adrenergic blockade would limit vasoconstriction during hyperoxia and increase FBF to levels observed under normoxic conditions. Nine male subjects (age 28 ± 1 yr) performed forearm exercise (20% of maximum) under normoxic and hyperoxic conditions. Studies were performed in a hyperbaric chamber at 1 atmosphere absolute (ATA; sea level) while breathing 21% O2 and at 2.82 ATA while breathing 100% O2 (estimated change in arterial O2 content ∼6 ml O2/100 ml). FBF (ml/min) was measured using Doppler ultrasound. Forearm vascular conductance (FVC) was calculated from FBF and blood pressure (arterial catheter). Vasoconstrictor responsiveness was determined using intra-arterial tyramine. FBF and FVC were substantially lower during hyperoxic exercise than normoxic exercise (∼20–25%; P < 0.01). At rest, vasoconstriction to tyramine (% decrease from pretyramine values) did not differ between normoxia and hyperoxia ( P > 0.05). During exercise, vasoconstrictor responsiveness was slightly greater during hyperoxia than normoxia (−22 ± 3 vs. −17 ± 2%; P < 0.05). However, during α-adrenergic blockade, hyperoxic exercise FBF and FVC remained lower than during normoxia ( P < 0.01). Therefore, our data suggest that although the vasoconstrictor responsiveness during hyperoxic exercise was slightly greater, it likely does not explain the majority of the large reductions in FBF and FVC (∼20–25%) during hyperbaric hyperoxic exercise.

We tested the hypothesis that elevated sympathetic tone is responsible for lower peak vasodilation after single muscle contractions in older adults. Young ( n = 13, 7 men and 6 women, age: 27 ± 1 yr) and older ( n = 13, 7 men and 6 women, age: 69 ± 2 yr) adults performed single forearm contractions at 10%, 20%, and 40% of maximum during 1) control, 2) sympathetic activation via lower body negative pressure (LBNP; −20 mmHg), and 3) intra-arterial infusion of phentolamine (α-adrenergic antagonist). Brachial artery diameter and velocities were measured via Doppler ultrasound, and forearm vascular conductance (FVC; in ml·min−1·100 mmHg−1) was calculated from blood flow (in ml/min) and blood pressure (in mmHg). Peak vasodilator responses [change in (Δ) FVC from baseline] were attenuated in older adults at 20% and 40% of maximum ( P < 0.05). LBNP reduced peak ΔFVC at 10% (98 ± 17 vs. 70 ± 12 ml·min−1·100 mmHg−1), 20% (144 ± 12 vs. 98 ± 3 ml·min−1·100 mmHg−1), and 40% (209 ± 20 vs. 161 ± 21 ml·min−1·100 mmHg−1, P < 0.01 vs. control) in younger adults but not in older adults (71 ± 11 vs. 68 ± 11, 107 ± 13 vs. 106 ± 16, and 161 ± 22 vs. 144 ± 22 ml·min−1·100 mmHg−1, respectively, P = 0.22–0.99). With phentolamine, peak ΔFVC was enhanced in older adults at each contraction intensity (100 ± 14, 147 ± 22, and 200 ± 26 ml·min−1·100 mmHg−1, respectively, P < 0.01 vs. control) but not in younger adults (94 ± 13, 153 ± 13, and 224 ± 27 ml·min−1·100 mmHg−1, respectively, P = 0.30–0.81 vs. control). Our data indicate that α-adrenergic vasoconstriction and/or blunted functional sympatholysis might contribute to the age-related decreases in skeletal muscle contraction-induced rapid vasodilation in humans.

Aging is associated with increased retrograde and oscillatory shear in peripheral conduit arteries of humans. Although the mechanisms responsible for these age-related changes are not completely understood, augmented downstream α-adrenergic tone likely plays a significant role in this phenomenon. Therefore, in protocol 1, brachial artery diameter and blood velocity were measured via Doppler ultrasound during (1) rest (control), (2) endogenous norepinephrine release via intra-arterial infusions of tyramine, and (3) α-adrenergic blockade via infusions of phentolamine in young healthy humans (n=12). Tyramine increased brachial artery retrograde (−4.0±1.4 to −9.5±1.4 s –1 ) and oscillatory shear (0.05±0.02 to 0.18±0.05 arbitrary units), whereas phentolamine abolished retrograde and oscillatory shear ( P <0.05). Additionally, in protocol 2, we examined brachial artery shear patterns in young (n=12; 29±2 years) and older (n=13; 69±2 years) healthy adults during (1) rest (control), (2) sympathetic activation via lower body negative pressure, and (3) infusion of phentolamine. At rest, older adults exhibited greater brachial artery retrograde and oscillatory shear (−9.9±2.7 s –1 and 0.11±0.03 arbitrary units, respectively) compared with younger adults (−3.1±1.0 s –1 and 0.05±0.02 arbitrary units, respectively; P <0.05 for both). Lower body negative pressure increased retrograde and oscillatory shear in young ( P <0.05), but not older adults ( P =0.85–0.97), such that differences between young and older were eliminated ( P >0.05). During infusion of phentolamine, retrograde and oscillatory shear were abolished in young adults ( P <0.05) and markedly reduced, yet still persistent, in older adults ( P <0.01). Our data indicate that α-adrenergic vasoconstriction is a major contributor to age-related discrepancies in conduit artery shear-rate patterns at rest.

The antihypertensive influence of fish oil is controversial, and the mechanisms remain unclear. Because the inverse relation between fish oil and hypertension appears to be partially dependent on the degree of hypertension, we tested the hypothesis that fish oil would elicit more dramatic reductions in mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA) in prehypertensive (PHT) compared with normotensive (NT) subjects. Resting MAP, MSNA, and heart rate (HR) were examined before and after 8 wk of fish oil (9 g/day; 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid) or placebo (olive oil; 9 g/day) in 38 NT (19 fish oil; 19 placebo) and 29 PHT (15 fish oil; 14 placebo) volunteers. Fish oil did not alter resting MAP, MSNA, or HR in either NT (80 ± 1 to 80 ± 1 mmHg; 11 ± 2 to 10 ± 1 bursts/min; 71 ± 2 to 71 ± 2 beats/min) or PHT (88 ± 2 to 87 ± 1 mmHg; 11 ± 2 to 10 ± 2 bursts/min; 73 ± 2 to 73 ± 2 beats/min) subjects. When NT and PHT groups were consolidated, analysis of covariance confirmed that pretreatment resting MAP was not associated with changes in MSNA after fish oil. In contrast, pretreatment resting HR was correlated with changes in MSNA ( r = 0.47; P = 0.007) and MAP ( r = 0.42; P < 0.007) after fish oil but not placebo. In conclusion, fish oil did not alter sympathetic neural control in NT or PHT subjects. However, our findings suggest that fish oil is associated with modest sympathoinhibition in individuals with higher resting heart rates, a finding that is consistent with a recent meta-analysis examining the relations among fish oil, HR, and the risk of cardiovascular disease.

Background —We tested sympathetic and cardiovagal baroreflex sensitivity during the placebo or “low-hormone” phase (LH) and 2 to 3 weeks later during the “high-hormone” phase (HH) of oral contraceptive (OC) use in 9 women. Methods and Results —Sympathetic baroreflex sensitivity was assessed by intravenous doses of sodium nitroprusside and phenylephrine and defined as the slope relating muscle sympathetic nerve activity (by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. No difference was observed for resting muscle sympathetic nerve activity or plasma norepinephrine levels. However, sympathetic baroreflex sensitivity was greater and mean arterial pressure was higher during the LH than in the HH phase. Similarly, cardiovagal baroreflex sensitivity was greater in the LH than in the HH phase. Conclusions —Sympathetic and cardiovagal baroreflex sensitivities change during the 28-day course of OC use. Furthermore, changes in baroreflex sensitivity with OC differ from changes in baroreflex sensitivity during the normal menstrual cycle.