Christopher E. Schwartz

Neurovascular responses to mental stress in prehypertensive humans

Neurovascular responses to mental stress have been linked to several cardiovascular diseases, including hypertension. Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and forearm vascular responses to mental stress are well documented in normotensive (NT) subjects, but responses in prehypertensive (PHT) subjects remain unclear. We tested the hypothesis that PHT would elicit a more dramatic increase of MAP during mental stress via augmented MSNA and blunted forearm vascular conductance (FVC). We examined 17 PHT (systolic 120-139 and/or diastolic 80-89 mmHg; 22 ± 1 yr) and 18 NT (systolic < 120 and diastolic < 80 mmHg; 23 ± 2 yr) subjects. Heart rate, MAP, MSNA, FVC, and calf vascular conductance were measured during 5 min of baseline and 5 min of mental stress (mental arithmetic). Mental stress increased MAP and FVC in both groups, but the increases in MAP were augmented (Δ 10 ± 1 vs. Δ14 ± 1 mmHg; P < 0.05), and the increases in FVC were blunted (Δ95 ± 14 vs. Δ37 ± 8%; P < 0.001) in PHT subjects. Mental stress elicited similar increases in MSNA (Δ7 ± 2 vs. Δ6 ± 2 bursts/min), heart rate (Δ21 ± 3 vs. Δ18 ± 3 beats/min), and calf vascular conductance (Δ29 ± 10 vs. Δ19 ± 5%) in NT and PHT subjects, respectively. In conclusion, mental stress elicits an augmented pressor response in PHT subjects. This augmentation appears to be associated with altered forearm vascular, but not MSNA, responses to mental stress.

Fish oil and neurovascular control in humans

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.

Sympathetic neural responses to mental stress during acute simulated microgravity

Neural and cardiovascular responses to mental stress and acute 6 degrees head-down tilt (HDT) were examined separately and combined. We hypothesized sympathoexcitation during mental stress, sympathoinhibition during HDT, and an additive neural interaction during combined mental stress and HDT. Muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded in 16 healthy subjects (8 men, 8 women) in the supine position during three randomized trials: 1) mental stress (via mental arithmetic), 2) HDT, and 3) combined mental stress and HDT. Mental stress significantly increased MSNA (7+/-1 to 12+/-2 bursts/min; P<0.01), MAP (91+/-2 to 103+/-2 mmHg; P<0.01), and HR (70+/-3 to 82+/-3 beats/min; P<0.01). HDT did not change MSNA or HR, but MAP was reduced (91+/-2 to 89+/-3 mmHg; P<0.05). Combined mental stress and HDT significantly increased MSNA (7+/-1 to 10+/-1 bursts/min; P<0.01), MAP (88+/-3 to 99+/-3 mmHg; P<0.01), and HR (70+/-3 to 82+/-3 beats/min; P<0.01). Increases in MSNA and HR during the combination trial were not different from the sum of the individual trials. However, the increase in MAP during the combination trial was significantly greater than the sum of the individual trials (change of 11+/-1 vs. 9+/-1 mmHg; P<0.05). We conclude that the interaction for MSNA and HR are additive during combined mental stress and HDT but that MAP responses are slightly augmented during the combined trial. These findings demonstrate that sympathetic neural responses to mental stress are unaltered by simulated microgravity.

Sympathetic neural reactivity to mental stress differs in black and non-Hispanic white adults

Black adults have a higher risk of hypertension compared with non-Hispanic white (NHW) adults, but physiological mechanisms underlying this predisposition remain unclear. This study compared muscle sympathetic nerve activity (MSNA) responses to mental stress in a group of young black and NHW participants. We hypothesized that the sympathoexcitation associated with mental stress would be greater in black adults compared with NHW participants. Thirty-five male adults (19 black, 23 ± 1 yr; 16 NHW, 22 ± 1 yr) were examined during 5-min supine baseline and 5 min of mental stress (via mental arithmetic). Baseline mean arterial pressure (80 ± 2 vs. 82 ± 1 mmHg), heart rate (61 ± 4 vs. 61 ± 2 beats/min), MSNA (13 ± 1 vs. 15 ± 2 bursts/min), and sympathetic baroreflex sensitivity (-1.1 ± 0.4 vs. -1.5 ± 0.3 bursts·100 heart beats-1·mmHg-1) were not significantly different between NHW and black adults ( P > 0.05), respectively. MSNA reactivity to mental stress was significantly higher in NHW compared with black adults (time × race, P = 0.006), with a particularly divergent responsiveness during the first minute of mental stress in NHW (Δ4 ± 1 burst/min) and black (Δ-2 ± 2 burst/min; P = 0.022) men. Blood pressure and heart rate reactivity to mental stress were similar between groups. In summary, black participants demonstrated a lower MSNA responsiveness to mental stress compared with NHW adults. These findings suggest that, despite a higher prevalence of hypertension, black subjects do not appear to have higher neural and cardiovascular responsiveness to mental stress compared with NHW. NEW & NOTEWORTHY Black men have a blunted muscle sympathetic nerve activity response to mental stress compared with non-Hispanic white (NHW) men, especially at the onset of mental stress when muscle sympathetic nerve activity decreased in blacks and increased in NHW men. Thus, despite a high prevalence of hypertension in blacks, normotensive NHW men display a greater peripheral sympathetic neural reactivity to mental stress than black men.

REDUCED CEREBRAL BLOOD FLOW WITH ORTHOSTASIS PRECEDES HYPOCAPNIC HYPERPNEA, SYMPATHETIC ACTIVATION AND POTS

Hyperventilation and reduced cerebral blood flow velocity can occur in postural tachycardia syndrome (POTS). We studied orthostatically intolerant patients, with suspected POTS, with a chief complaint of upright dyspnea. On the basis of our observations of an immediate reduction of cerebral blood flow velocity with orthostasis, we hypothesize that the resulting ischemic hypoxia of the carotid body causes chemoreflex activation, hypocapnic hyperpnea, sympathetic activation, and increased heart rate and blood pressure in this subset of POTS. We compared 11 dyspneic POTS subjects with 10 healthy controls during a 70° head-up tilt. In POTS subjects during initial orthostasis before blood pressure recovery; central blood volume and mean arterial pressure were reduced (P<0.025), resulting in a significant (P<0.001) decrease in cerebral blood flow velocity, which temporally preceded (17±6 s; P<0.025) a progressive increase in minute ventilation and decrease in end tidal CO2 (P<0.05) when compared with controls. Sympathoexcitation, measured by muscle sympathetic nerve activity, was increased in POTS (P<0.01) and inversely proportional to end tidal CO2 and resulted in an increase in heart rate (P<0.001), total peripheral resistance (P<0.025), and a decrease in cardiac output (P<0.025). The decrease in cerebral blood flow velocity and mean arterial pressure during initial orthostasis was greater (P<0.025) in POTS. Our data suggest that exaggerated initial central hypovolemia during initial orthostatic hypotension in POTS results in reduced cerebral blood flow velocity and postural hypocapnic hyperpnea that perpetuates cerebral ischemia. We hypothesize that sustained hypocapnia and cerebral ischemia produce sympathoexcitation, tachycardia, and a statistically significant increase in blood pressure.