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 [69±1 (mean±SEM) years] and 31 women (68±1 years). Carotid artery stiffness (B-mode ultrasonography) and aortic stiffness (magnetic resonance imaging) were also determined. We found that elderly women had lower sympathetic baroreflex sensitivity than elderly men (–2.33±0.25 vs. –3.32±0.25 bursts·100 beats–1·mmHg–1; P=0.007). β-stiffness indices of the carotid artery and the aorta were greater in elderly women than in men (6.68±0.48 vs. 5.10±0.50 and 4.03±0.47 vs. 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), while this relation was shifted in parallel upward (towards a reduced sensitivity) in women with no changes in the slope (0.26 vs. 0.24 a.u.). 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.

Key points• 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.• 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.• 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.• It is suggested that sympathetic activation is a common characteristic of early pregnancy in normotensive women.• These results help us better understand blood pressure control mechanisms during normal pregnancy in humans.Abstract 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. 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. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min −1 , 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min −1 ; main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm −5 ; P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.−1 min −1 ; P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml −1 , P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml −1 , P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.

This study aimed to quantify the directional specificity of multidirectional lip-closing force (LCF) and evaluate the reliability of multidirectional LCF measurements made using a novel system. In fourteen healthy subjects (seven females, seven males, median age = 28 years), LCFs in eight directions and electromyograms (EMGs) from four parts of the orbicularis oris muscles (OOM) were recorded during voluntary pursing-like lip closure tasks. The quantitative reliability was assessed from repeated measurements of the LCFs in the eight directions and from summed values for all eight directions [total lip-closing force (TLCF)]. The intra- and inter-investigator reliabilities for TLCF were assessed by the interclass correlation of the measurements by the same investigator and two investigators, respectively. Lip-closing forces showed directional specificity in vertical, horizontal and oblique directions but those in oblique and horizontal directions were symmetrical bilaterally. The quantitative reliability of measurements was between 0·735 and 0·948 in the eight directions and that of TLCF was 0·934. Interclass correlations of intra- and inter-investigator reliabilities were 0·96 [lower limit of 95% confidence interval (95% LL), 0·87] and 0·96 (95% LL, 0·91), respectively. The intra- and inter-investigator differences of measurements were randomly distributed in the whole range of measurements. The 95% confidence intervals of these differences were significantly narrower than those of the limits of agreement (mean ± 1·96 s.d.). In 13 subjects, Pearson's correlation coefficients between LCF and EMGs from OOM were above 0·95. We conclude that this system has a reasonable quality and reliability for quantitative measurements of multidirectional LCF for evaluating lip functions.

High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS) is an emerging application for the comprehensive and detailed analysis of the spatial distribution of ionized molecules in situ on tissue slides. HR-MALDI-IMS in negative mode in a mass range of m/z 500–1000 was performed on optimal cutting temperature (OCT) compound-embedded human prostate tissue samples obtained from patients with prostate cancer at the time of radical prostatectomy. HR-MALDI-IMS analysis of the 14 samples in the discovery set identified 26 molecules as highly expressed in the prostate. Tandem mass spectrometry (MS/MS) showed that these molecules included 14 phosphatidylinositols (PIs), 3 phosphatidylethanolamines (PEs) and 3 phosphatidic acids (PAs). Among the PIs, the expression of PI(18:0/18:1), PI(18:0/20:3) and PI(18:0/20:2) were significantly higher in cancer tissue than in benign epithelium. A biomarker algorithm for prostate cancer was formulated by analyzing the expression profiles of PIs in cancer tissue and benign epithelium of the discovery set using orthogonal partial least squares discriminant analysis (OPLS-DA). The sensitivity and specificity of this algorithm for prostate cancer diagnosis in the 24 validation set samples were 87.5 and 91.7%, respectively. In conclusion, HR-MALDI-IMS identified several PIs as being more highly expressed in prostate cancer than benign prostate epithelium. These differences in PI expression profiles may serve as a novel diagnostic tool for prostate cancer.

HR-MALDI-IMS showed that the expression of LPC(16:0/OH) and SM(d18:1/16:0) was lower in prostate cancer than in benign prostate epithelium. These differences in expression of phospholipids may predict prostate cancer aggressiveness, and provide new insights into lipid metabolism in prostate cancer.

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.

Corin (an atrial natriuretic peptide converting enzyme) represents a potential biomarker for gestational hypertensive disorders; yet, its role in blood pressure regulation throughout pregnancy remains unclear. We investigated the time-course of change in blood corin content in relation to blood pressure and sympathetic nerve activity throughout pregnancy. Forty-four women (29±0.9 yrs) participated. Following-term, 23 had 'low-risk' (no personal history of gestational hypertensive disorders) normal pregnancies, 13 had 'high-risk' (personal history of gestational hypertensive disorders) normal pregnancies, and eight developed gestational hypertension. Blood pressure, heart rate, muscle sympathetic nerve activity, and serum corin were measured prior-to pregnancy, during early-(4-8 wks) and late-pregnancy (32-36 wks), and post-partum (6-10 wks). Overall, compared to pre-pregnancy, corin remained unchanged during early-pregnancy, increased markedly during late-pregnancy (P<0.001), and returned to pre-pregnancy levels post-partum. In women who developed gestational hypertension, the change in corin from early-to late-pregnancy was greater than those with 'low-risk' normal pregnancies (Δ971±134 vs. Δ486±79 pg/mL; P<0.05). Throughout pregnancy, blood pressure and muscle sympathetic nerve activity were augmented in women with gestational hypertension (all P<0.05). Finally, changes in corin from early-to late-pregnancy were related to all indices of blood pressure (R=0.454-0.551; all P<0.01) in late-pregnancy, whereas burst frequency, burst incidence, and total muscle sympathetic nerve activity (R=0.576-0.614; all P<0.001) in early-pregnancy were related to changes in corin from early-to late-pregnancy. Corin plays a unique role in blood pressure regulation throughout

Non-technical summary Thermoregulatory responses during exercise are reduced following thermal dehydration. If individuals do not rehydrate adequately, it could lead to heat exhaustion or stroke with the worst case scenario being death. Plasma volume loss during dehydration has been suggested to suppress cutaneous vasodilatation in response to hyperthermia via a baroreflex-mediated reduction in active vasodilator activity rather than enhanced active vasoconstrictor activity. However, no changes in the electrical signals of the efferent neural pathway have ever been identified. In the present study, we found a component of efferent skin sympathetic nerve activity that was synchronized with the cardiac cycle in thermally stressed individuals. This nerve activity increased with an increase in oesophageal temperature and the increase was significantly suppressed by hypovolaemia. Thus, this component of skin sympathetic nerve activity might represent the active vasodilator signals that regulate skin blood flow during hyperthermia in humans.Abstract Although cutaneous vasodilatation in hyperthermia was suppressed during hypovolaemia, the efferent neural pathway mediating this suppression has not been identified. To determine the electrical nerve signals which account for the suppression of cutaneous vasodilatation during hypovolaemia, skin sympathetic nerve activity (SSNA; microneurography) from the peroneal nerve, laser-Doppler blood flow (LDF) on the ipsilateral dorsal foot, mean arterial pressure (MAP; sonometry) and oesophageal temperature (T oes ) were measured before and during 45 min of passive warming in 20 healthy subjects during normovolaemia (n = 10) or hypovolaemia (n = 10) conditions. Hypovolaemia was achieved by diuretic administration. Cutaneous vascular conductance (CVC = LDF/MAP), SSNA burst frequency and total SSNA obtained from rectified and filtered SSNA signal increased as T oes increased by ∼0.5 • C by the end of warming in both groups. The increase in CVC was significantly lower in hypovolaemia than normovolaemia (P < 0.0001), but with no significant difference in the increase in burst frequency and total SSNA between groups (P > 0.32). However, using an alternative analysis that constructed spike incidence histograms from the original signal using 0.05 s bins during the 5 s following a given R-wave, we found a SSNA component synchronized with the cardiac cycle with a 1.1-1.3 s latency. This component increased with an increase in T oes and the increase was significantly suppressed by hypovolaemia (P < 0.0001). In conclusion, hypovolaemic suppression of cutaneous vasodilatation during hyperthermia might be caused by a reduction in the SSNA component synchronized with cardiac cycle. , plasma noradrenaline concentration; P osmol , plasma osmolality; PP, pulse pressure; PV, plasma volume; RH, relative humidity; RR, respiratory rate; SBP, systolic blood pressure; SkBF, skin blood flow; SR, sweat rate; SSNA, skin sympathetic nerve activity; T a , ambient temperature; T oes , oesophageal temperature;...