Sara S. Jarvis

Relationship Between Sympathetic Baroreflex Sensitivity and Arterial Stiffness in Elderly Men and Women

Previous human studies have shown that large-artery stiffness contributes to an age-related decrease in cardiovagal baroreflex sensitivity. Whether this is also true with sympathetic baroreflex sensitivity is unknown. We tested the hypothesis that sympathetic baroreflex sensitivity is associated with the stiffness of baroreceptor segments (the carotid artery and the aorta) in elderly individuals and that sex affects this relationship. Sympathetic baroreflex sensitivity was assessed from the spontaneous changes in beat-by-beat diastolic pressure and corresponding muscle sympathetic nerve activity (microneurography) during supine rest in 30 men (mean±SEM: 69±1 years) and 31 women (68±1 years). Carotid artery stiffness (B-mode ultrasonography) and aortic stiffness (MRI) were also determined. We found that elderly women had lower sympathetic baroreflex sensitivity than elderly men (−2.33±0.25 versus −3.32±0.25 bursts · 100 beats−1 · mm Hg−1; P=0.007). &bgr;-Stiffness indices of the carotid artery and the aorta were greater in elderly women than in men (6.68±0.48 versus 5.10±0.50 and 4.03±0.47 versus 2.68±0.42; both P<0.050). Sympathetic baroreflex sensitivity was inversely correlated with carotid artery stiffness in both men and women (r=0.49 and 0.50; both P<0.05), whereas this relation was shifted in parallel upward (toward a reduced sensitivity) in women with no changes in the slope (0.26 versus 0.24 arbitrary units). Sympathetic baroreflex sensitivity and aortic stiffness showed similar trends. Thus, barosensory artery stiffness seems to be one independent determinant of sympathetic baroreflex sensitivity in elderly men and women. The lower sympathetic baroreflex sensitivity in elderly women may predispose them to an increased prevalence of hypertension.

Sympathetic activation during early pregnancy in humans

•u2002 Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. •u2002 Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. •u2002 We found that vasomotor sympathetic activity was markedly greater, diastolic pressure trended lower, total peripheral resistance decreased, sympathetic vascular transduction was blunted, and renin and aldosterone both were higher during early pregnancy (i.e. ≤8 weeks of gestation) than pre‐pregnancy. •u2002 It is suggested that sympathetic activation is a common characteristic of early pregnancy in normotensive women. •u2002 These results help us better understand blood pressure control mechanisms during normal pregnancy in humans.

Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans

Sex differences in sympathetic neural control during static exercise in humans are few and the findings are inconsistent. We hypothesized women would have an attenuated vasomotor sympathetic response to static exercise, which would be further reduced during the high sex hormone [midluteal (ML)] vs. the low hormone phase [early follicular (EF)]. We measured heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) in 11 women and 10 men during a cold pressor test (CPT) and static handgrip to fatigue with 2 min of postexercise circulatory arrest (PECA). HR increased during handgrip, reached its peak at fatigue, and was comparable between sexes. BP increased during handgrip and PECA where men had larger increases from baseline. Mean ± SD MSNA burst frequency (BF) during handgrip and PECA was lower in women (EF, P < 0.05), as was ΔMSNA-BF smaller (main effect, both P < 0.01). ΔTotal activity was higher in men at fatigue (EF: 632 ± 418 vs. ML: 598 ± 342 vs. men: 1,025 ± 416 a.u./min, P < 0.001 for EF and ML vs. men) and during PECA (EF: 354 ± 321 vs. ML: 341 ± 199 vs. men: 599 ± 327 a.u./min, P < 0.05 for EF and ML vs. men). During CPT, HR and MSNA responses were similar between sexes and hormone phases, confirming that central integration and the sympathetic efferent pathway was comparable between the sexes and across hormone phases. Women demonstrated a blunted metaboreflex, unaffected by sex hormones, which may be due to differences in muscle mass or fiber type and, therefore, metabolic stimulation of group IV afferents.

Morning blood pressure surge is associated with arterial stiffness and sympathetic baroreflex sensitivity in hypertensive seniors

Morning blood pressure (BP) surge is considered to be an independent risk factor for cardiovascular diseases. We tested the hypothesis that increased large-artery stiffness and impaired sympathetic baroreflex sensitivity (BRS) contribute to augmented morning surge in elderly hypertensive subjects. Morning surge was assessed as morning systolic BP averaged for 2 h just after waking up minus minimal sleeping systolic BP by using ambulatory BP monitoring (ABPM) in 40 untreated hypertensive [68 ± 1 (SE) yr] and 30 normotensive (68 ± 1 yr) subjects. Beat-by-beat finger BP and muscle sympathetic nerve activity (MSNA) were recorded in the supine position and at 60° upright tilt. We assessed arterial stiffness with carotid-to-femoral pulse wave velocity (cfPWV) and sympathetic BRS during spontaneous breathing. Awake and asleep ABPM-BPs and morning surge were higher in hypertensive than normotensive subjects (all P < 0.001). cfPWV was higher (P = 0.002) and sympathetic BRS was lower (P = 0.096) in hypertensive than normotensive subjects. Hypertensive subjects with morning surge ≥35 mmHg (median value) had higher cfPWV (11.9 ± 0.5 vs. 9.9 ± 0.4 m/s, P = 0.002) and lower sympathetic BRS (supine: -2.71 ± 0.25 vs. -3.73 ± 0.29, P = 0.011; upright: -2.62 ± 0.22 vs. -3.51 ± 0.35 bursts·100 beats(-1)·mmHg(-1), P = 0.052) than those with morning surge <35 mmHg. MSNA indices were similar between groups (all P > 0.05), while upright total peripheral resistance was higher in hypertensive subjects with greater morning surge than those with lesser morning surge (P = 0.050). Morning surge was correlated positively with cfPWV (r = 0.59, P < 0.001) and negatively with sympathetic BRS (r = 0.51, P < 0.001) in hypertensive subjects only. Thus, morning BP surge is associated with arterial stiffness and sympathetic BRS, as well as vasoreactivity during orthostasis in hypertensive seniors.

Asian women have attenuated sympathetic activation but enhanced renal-adrenal responses during pregnancy compared to Caucasian women.

Asian women have a lower prevalence of hypertensive disorders of pregnancy than Caucasian women. This is the first longitudinal study to investigate neural and humoral responses during pregnancy in Asians and Caucasians. The key finding was that Asians had attenuated sympathetic activation but enhanced renal–adrenal responsiveness during pregnancy compared to Caucasians. These results may provide insights into the pathophysiological mechanisms for racial differences in the prevalence of hypertensive disorders during pregnancy.

Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors

•u2002 Cardiovascular risk remains high in elderly patients with hypertension even with adequate blood pressure control; one possible mechanism may be sympathetic activation via the baroreflex in response to blood pressure reduction. •u2002 We found that chronic diuresis increased vasomotor sympathetic activity in both the supine and the upright positions, while chronic renin inhibition did not affect sympathetic activity in the supine position but attenuated its response to head‐up tilt in elderly hypertensive patients. •u2002 The change of sympathetic activity by anti‐hypertensive drug treatment was correlated with the change of aldosterone level in all patients. •u2002 Upright sympathetic baroreflex sensitivity remained unchanged after diuresis or renin inhibition. •u2002 These results suggest that chronic renin inhibition lowers blood pressure in elderly hypertensive patients without sympathetic activation, in contrast to diuresis which increases sympathetic activity through the augmented renin–angiotensin–aldosterone system.

Age and sex differences in muscle sympathetic nerve activity in relation to haemodynamics, blood volume and left ventricular size

What is the central question of this study? The study was designed to investigate the age‐ and sex‐related differences in muscle sympathetic nerve activity (MSNA) in relation to age‐ and sex‐related differences in haemodynamics, blood volume and left ventricular size and function. What is the main finding and its importance? Age‐related increases in MSNA were associated with decreases in blood volume in men only, and only in men was there a significant relation between MSNA and forearm vascular resistance. These results show that age and sex independently alter the neural control of blood pressure and may provide insights into the pathogenesis of hypertension.

Elderly Blacks Have a Blunted Sympathetic Neural Responsiveness But Greater Pressor Response to Orthostasis Than Elderly Whites

Neural control of blood pressure (BP) has been reported to differ between young blacks and whites. We hypothesized that elderly blacks have enhanced sympathetic neural responses during orthostasis compared with elderly whites. Muscle sympathetic nerve activity, arm-cuff BP, and heart rate were recorded continuously, and cardiac output, stroke volume, and total peripheral resistance were measured intermittently during supine and 5-minute 60° upright tilt in 10 blacks (65 [SD, 4] years; 4 women) and 20 whites (68 [6] years; 8 women). We found that muscle sympathetic nerve activity burst frequency was similar between blacks and whites in the supine position (44 [10] versus 42 [7] bursts per minute) and during upright tilt (59 [11] versus 60 [9] bursts per minute; P=0.846 for race, P<0.001 for posture, and P=0.622 for interaction). However, upright total muscle sympathetic nerve activity was smaller in blacks than in whites (162 [39] versus 243 [112]%; P=0.003). Systolic BP, heart rate, cardiac output, and stroke volume were not different between groups. Diastolic BP was similar in the supine position, increased in all of the subjects during tilting; upright diastolic BP was greater in blacks than in whites (80 [10] versus 71 [7] mmHg; P=0.008). Total peripheral resistance did not differ between blacks and whites in the supine position or during upright tilt (P=0.354 for race, P<0.001 for posture, P=0.825 for interaction). Thus, elderly blacks have a blunted sympathetic neural responsiveness but enhanced pressor response to orthostasis compared with elderly whites, which may be attributable to an augmented sympathetic vascular transduction and/or nonadrenergic vasoconstrictor mechanisms (ie, angiotensin II or the venoarteriolar response).

Neural-humoral responses during head-up tilt in healthy young white and black women

Young black women have higher prevalence of hypertension during pregnancy compared to white women, which may be attributable to differences in blood pressure (BP) regulation. We hypothesized that young normotensive black women would demonstrate augmented muscle sympathetic nerve activity (MSNA) and renal-adrenal responses to orthostasis. Fifteen white and ten black women (30 ± 4 vs. 32 ± 6 years; means ± SD) had haemodynamics and MSNA measured during baseline (BL), 30 and 60° head-up tilt (HUT), and recovery. Blood was drawn for catecholamines, direct renin, vasopressin, and aldosterone. BL brachial systolic BP (SBP: 107 ± 6 vs. 101 ± 9 mmHg) and diastolic BP (DBP: 62 ± 4 vs. 56 ± 7 mmHg) were higher in white women (both p < 0.05). Δ DBP (60° HUT-BL) was greater in black women compared to white (p < 0.05). Cardiac output and total peripheral resistance were similar between groups. MSNA burst frequency was higher in whites (BL: 16 ± 10 vs. 14 ± 9 bursts/min, main effect p < 0.05) and increased in both groups during HUT (60°: 39 ± 8 vs. 34 ± 13 bursts/min, p < 0.05 from BL). Noradrenaline was higher in white women during 60° HUT (60° HUT: 364 ± 102 vs. 267 ± 89 pg/ml, p < 0.05). Direct renin was higher and vasopressin and Δ aldosterone tended to be higher in blacks (BL, direct renin: 12.1 ± 5.0 vs. 14.4 ± 3.7 pg/ml, p < 0.05; BL, vasopressin: 0.4 ± 0.0 vs. 1.6 ± 3.6 pg/ml, p = 0.065; Δ aldosterone: −0.9 ± 5.1 vs. 3.8 ± 7.5 ng/ml; p = 0.069). These results suggest that young normotensive white women may rely on sympathetic neural activity more so than black women who have a tendency to rely on the renal-adrenal system to regulate BP during an orthostatic stress.

Sympathetic Neural and Hemodynamic Responses During Cold Pressor Test in Elderly Blacks and Whites

The sympathetic response during the cold pressor test (CPT) has been reported to be greater in young blacks than whites, especially in those with a family history of hypertension. Because blood pressure (BP) increases with age, we evaluated whether elderly blacks have greater sympathetic activation during CPT than age-matched whites. BP, heart rate, cardiac output, and muscle sympathetic nerve activity were measured during supine baseline, 2-minute CPT, and 3-minute recovery in 47 elderly (68±7 [SD] years) volunteers (12 blacks and 35 whites). Baseline BP, heart rate, cardiac output, or muscle sympathetic nerve activity did not differ between races. Systolic and diastolic BP and heart rate increased during CPT (all P<0.001) with no racial differences (all P>0.05). Cardiac output increased during CPT and ⩽30 s of recovery in both groups, but was lower in blacks than whites. Muscle sympathetic nerve activity increased during CPT in both groups (both P<0.001); the increase in burst frequency was similar between groups, whereas the increase in total activity was smaller in blacks (P=0.030 for interaction). Peak change (&Dgr;) in diastolic BP was correlated with &Dgr; total activity at 1 minute into CPT in both blacks (r=0.78, P=0.003) and whites (r=0.43, P=0.009), whereas the slope was significantly greater in blacks (P=0.007). Thus, elderly blacks have smaller sympathetic and central hemodynamic (eg, cardiac output) responses, but a greater pressor response for a given sympathetic activation during CPT than elderly whites. This response may stem from augmented sympathetic vascular transduction, greater sympathetic activation to other vascular bed(s), or enhanced nonadrenergically mediated vasoconstriction in elderly blacks.