American journal of physiology. Regulatory, integrative and comparative physiology最新文献

Arterial stiffness is a well-known risk factor for cardiovascular disease. Although estradiol (E2) is known to be cardioprotective, the available data point to a growing cardiovascular disease risk in women before menopause due to posttraumatic stress disorder (PTSD). The present study aimed to investigate the effects of E2 on arterial compliance in trauma-exposed premenopausal women, with and without a clinical diagnosis of PTSD. We hypothesized that E2 will be differentially associated with pulse wave velocity (PWV) in women with PTSD (PTSD⁺, n = 45) and without PTSD (PTSD^-, n = 47). Estradiol and PWV were measured during two separate study visits. Serum E2 levels were measured via the quantitative sandwich enzyme-linked immunoassay technique (ELISA) and log-transformed due to non-normal distribution. Carotid to femoral applanation tonometry was used to measure PWV. Our analyses revealed an overall weak and nonsignificant correlation between E2 and PWV (r = -0.119, P = 0.350). However, when examining each group, we found a negative association between E2 and PWV in PTSD^- (r = -0.466, P = 0.004). In contrast, we found an unexpected positive association between E2 levels and PWV in PTSD⁺ (r = 0.360, P = 0.037). Furthermore, a multiple linear regression revealed that E2 was predictive of PWV in PTSD^- only, even after accounting for the phase of the menstrual cycle, age, body mass index, diastolic blood pressure, and PTSD symptom severity (R² = 0.670, P = 0.005). Interestingly, we also found lower levels of E2 in PTSD⁺ than PTSD^- (1.4 ± 0.4 vs. 1.6 ± 0.4 pg/mL, P = 0.022). These findings suggest that PTSD may inhibit the protective effects of E2 on arterial compliance in women before menopause.NEW & NOTEWORTHY In trauma-exposed premenopausal women, we found that serum estradiol (E2) was a predictor of pulse wave velocity (PWV) only in the absence of a posttraumatic stress disorder (PTSD) diagnosis, even after accounting for the phase of the menstrual cycle, age, body mass index, diastolic blood pressure, and PTSD symptom severity. Moreover, E2 levels were lower in women with PTSD than in those without PTSD. We collected E2 and PWV during two separate visits and controlled for the menstrual cycle phase in our analyses.

Persistent stressful situations can have detrimental cardiovascular effects; however, effects on the blood pressure (BP) response to exercise have not been fully examined. This study investigated the impact of a 2-wk stressful situation on the exercise pressor response. Eight healthy male university paramedic trainees underwent a 2-wk paramedic hospital training and a control period study. Pre- and postintervention, BP responses to the exercise test [2-min submaximal isometric handgrip (IHG) exercise followed by postexercise muscle ischemia (PEMI)] and cold pressure test (CPT) were assessed. A stress biomarker, salivary α-amylase (sAA) activity, significantly increased after hospital training (Pre: 8.8 ± 4.6; Post: 15.5 ± 7.3 kU/L; P = 0.036), whereas no significant changes were observed in the control period (Pre: 11.3 ± 3.6; Post: 10.4 ± 4.5 kU/L). Although no significant trial (hospital training vs. control)-by-intervention (pre- vs. post-2-wk period) interactions were detected in the mean arterial pressure (MAP) response to PEMI or CPT, a significant interaction in the MAP response to IHG exercise was noted (Δ48.9 ± 11.2 to Δ55.5 ± 9.1 mmHg, hospital training; Δ53.2 ± 14.1 to Δ51.2 ± 11.9 mmHg, control; P = 0.035). Consequently, changes in the sAA and MAP preintervention to postintervention showed a significant correlation (τ = 0.397, P = 0.036). Results showed that stressful paramedic hospital training augmented BP response to IHG exercise. This suggests that prolonged stressful situations increase pressor response to exercise, particularly in cases involving healthy young men.NEW & NOTEWORTHY Exposure to prolonged stressful situations augmented the blood pressure response to submaximal isometric exercise in healthy young men. This finding suggests that monitoring cardiovascular responses during exercise under chronic stress conditions could be important.

The purpose of this study was to investigate the effect of oral contraceptive pill (OCP) phase on in vivo microvascular endothelium-dependent vasodilation and contributions of nitric oxide (NO), cyclooxygenase (COX), and endothelial-derived hyperpolarizing factors (EDHF). Participants completed two experimental visits in random order, during the 1) low and 2) high hormone phase of the OCP cycle. Endothelium-dependent dilation was assessed in the cutaneous microvasculature via local heating at four intradermal microdialysis sites treated with: 1) lactated Ringer's (control), 2) 10 mM ketorolac (Keto, COX inhibitor), 3) 50 mM tetraethylammonium (TEA, calcium-activated potassium channel inhibitor), and 4) 10 mM ketorolac + TEA (Keto+TEA). Perfusion of 20 mM L-NAME at each site was used to quantify the L-NAME sensitive component of dilation, suggesting NO contribution. There was no effect of OCP phase on endothelium-dependent dilation (p=0.75) or the L-NAME sensitive component of the response (p=0.09, d=0.7) at control sites. Inhibition of COX increased baseline blood flow regardless of OCP phase (all p<0.01). Control and Keto sites elicited greater endothelium-dependent dilation than TEA and Keto+TEA sites in both phases (all p<0.0001). During the low hormone phase, the L-NAME sensitive component was greater at control compared with TEA sites (p<0.01). During the high hormone phase, the L-NAME sensitive component was greater at Keto compared with TEA sites (p<0.01). Within-participant differences between control and Keto sites support a phase-dependent restraint of NO activity via COX pathways (p=0.01). These findings demonstrate that the OCP phase affects underlying mechanistic pathways contributing to cutaneous microvascular endothelial function.

Fluid volume and osmolality balance are maintained by complex neuroendocrine and liquid-salt intake behavior, cardiovascular and renal mechanisms, and gastrointestinal adjustments. Mechanical stretching of the right atrium (AS) enhances central venous pressure and heart rate while decreasing gastric emptying (GE) of liquid in rats. We evaluated the effect of AS on GE and plasma levels of atrial natriuretic peptide (ANP), oxytocin (OT), and corticosterone (CORT) to determine whether ANP contributes to the OT-mediated GE delay of liquids due to AS in awake rats. Initially, we performed thoracotomy followed by right appendectomy (AX) or sham thoracotomy. One week later, rats were randomly subjected for pretreatment with NaCl 0.15 M (control), atosiban (AT, OT-antagonist), anantin (ANT, ANP-antagonist), or dexamethasone (DEX). Afterward, 50 µL of AS was administered for 5 min or not (sham). Then, the rats were fed a test meal, and GE of liquids or solids was performed. The other animals were pretreated with NaCl 0.15 M, atosiban, anantin, or dexamethasone, followed by OT treatment for GE assessment. Compared to the sham group, 50 µL of AS decreased the GE of the liquid and solid test meals. This phenomenon was prevented by AT, ANT, DEX, and surgical procedure with AX. AS also increased plasma levels of ANP, OT, and CORT. In turn, oxytocin treatment decreased GE and increased plasma ANP, OT and CORT levels, while AT, ANT and DEX prevented OT-induced GE delay. Hence, AS delayed GE of liquid in rats, a phenomenon that involves oxytocinergic pathways and ANP activity.

Chronic exposure to low oxygen (hypoxia) leads to amplification of the hypoxic chemoreflex, increasing breathing and sympathetic nervous system (SNS) activation. Prolonged SNS activation redistributes blood to hypoxia-sensitive tissues, away from muscles. Recent tracking studies have shown that migratory songbirds can fly 5,000 m or higher above sea level, leading us to hypothesize that migratory birds may have a blunted hypoxic chemoreflex to maintain blood flow to muscles during migratory flight at high altitudes. To test this hypothesis, we used a hypobaric wind tunnel and measured circulating plasma catecholamines after maximal altitude flight, flight at 75% of maximal altitude, flight at ground level (~250 m), and after rest at 75% of maximal altitude and ground level in migratory myrtle yellow-rumped warblers (Setophaga coronata). Yellow-rumped warblers were capable of flying above 4,000 m simulated altitude above sea level (average maximum altitude of ~3,600 m), and would maintain flights at 75% of individual maximum altitudes (~2,700 m). Circulating dopamine and noradrenaline were similar between resting and flight conditions at ground level and with exposure to 75% of maximal altitude, whereas adrenaline significantly increased with flight, but did not change further with flight at 75% of maximal altitude. By contrast, both adrenaline and noradrenaline concentrations increased after maximum altitude flights compared to 75% and ground level flights. Our findings show that exercise increases plasma adrenaline in migratory songbirds, and suggest that warblers flying at high altitudes below their maximum altitude may be minimally hypoxic, allowing them to maintain oxygen transport to flight muscles.

Fetal cerebral blood flow increases in response to acute hypoxia, mediated in part by an adrenergic α1 receptor (α1-R)-mediated increase in peripheral vascular resistance that redirects cardiac output to the brain. Activation of cerebral α1-R may attenuate the increase in cerebral blood flow during hypoxia, and this effect may be even greater in fetuses exposed to chronic high-altitude hypoxia, previously shown to increase the contractile function of cerebral artery α1-Rs. We hypothesized that α1-R activation in the fetal sheep brain attenuates increases in cerebral blood flow during acute hypoxia and that this effect would be accentuated in fetuses exposed to chronic hypoxia. Near-term fetal sheep gestated at low or high altitude (3801 m) were instrumented chronically for measurement of mean arterial pressure (MAP), heart rate (HR), cerebral cortical blood flow (CBF), and cortical vascular resistance (CVR). Responses to acute hypoxia were then measured in the presence and absence of prazosin (α1-R antagonist). Prazosin infusion resulted in a decrease in baseline MAP and CBF. During acute hypoxia, CBF increased by only 14±6% above baseline in the prazosin group, compared to 28±9% in the vehicle group (Fig. 1), with no significant difference in CVR in either group. Similar to the low altitude animals, prazosin did not significantly alter the CBF or CVR response to acute hypoxia, nor recovery following acute hypoxia, in the high altitude fetuses. We conclude that cortical α1-Rs neither attenuate increased CBF during acute hypoxia, nor mediate the cortical vasoconstriction that occurs in recovery from acute hypoxia.

Nitric oxide synthase (NOS) is an important mediator of cutaneous vasodilation during exercise-heat stress. We recently reported that pharmacological activation of transient receptor potential ankyrin 1 (TRPA1) channel mediates cutaneous vasodilation via NOS-dependent mechanisms under non-heat stress resting conditions. Here, we hypothesized that TRPA1 channel activation would contribute to cutaneous vasodilation during exercise in the heat via NOS-dependent mechanisms. To assess this response, we first conducted TRPA1 channel antagonist verification sub-study (10 young adults, 5 women) wherein 1 mM ASP7663 (TRPA1 channel agonist) increased cutaneous vascular conductance (CVC; cutaneous blood flow divided by mean arterial pressure), and this response was blocked by ~50% with 100 μM HC030031, a known TRPA1 channel antagonist. Subsequently, twelve young adults (5 women) completed two bouts of 30-min moderate-intensity cycling (45% of their predetermined peak oxygen uptake) in the heat (35°C). During the first exercise, CVC was evaluated at four dorsal forearm skin sites perfused with a 5%DMSO, while in the second bout, all sites were treated with either 1) a 5% DMSO (control), 2) 100μM HC030031, 3) 20 mM L-NAME, a non-selective NOS inhibitor, or 4) combination of both. No between-site differences in CVC were measured during the first exercise (P>0.182). During the second exercise, HC030031 alone had no effect on CVC relative to the control (all P>0.104). Both L-NAME and HC030031 + L-NAME reduced CVC (all P<0.001), with the combined treatment showing a greater reduction (all P<0.001). We showed that TRPA1 channels mediate cutaneous vasodilation during exercise-heat stress only when NOS is inhibited.

This study examined potential sex differences on performance and perceived fatigability during a whole-body endurance exercise performed under normoxia or moderate hypoxia. Nine male and eight female cyclists performed a 4-km cycling time-trial under normoxia or hypoxia conditions. Performance fatigability and its central and peripheral determinants were measured via pre- to post-exercise changes in maximal voluntary isometric contraction (IMVC), voluntary activation (VA), and potentiated twitch force (TwPt) of knee extensors, respectively. Perceived fatigability was characterized via rating of perceived exertion (RPE). Time to complete the trial was longer in hypoxia than normoxia in females (482 ± 24 vs 465 ± 21 s) and males (433 ± 30 vs 408 ± 31 s) (P = 0.039). There was no effect of sex or condition (P ≥ 0.370) for the magnitude of decrease in IMVC (female: normoxia = -14.3 ± 4.4 %, hypoxia = -11.8 ± 5.2 % vs male: normoxia = -13.1 ± 9.4 %, hypoxia = -12.9 ± 9.8 %), TwPt (female: normoxia = -34.4 ± 11.4 %, hypoxia = -31.8 ± 18.9 % vs male: normoxia = -30.5 ± 17.9 %, hypoxia = -31.9 ± 20.9 %), and VA (female: normoxia = -0.5 ± 2.3 %, hypoxia = -1.6 ± 1.6 % vs male: normoxia = 0.8 ± 2.2 %, hypoxia = -0.5 ± 1.3 %). RPE was higher in hypoxia than normoxia for both groups (P = 0.002). In conclusion, moderate hypoxia similarly impairs performance and perceived fatigability development in females and males during a 4-km cycling time-trial.

Saliva plays a crucial role in digestion, including taste perception, food breakdown, chewing, swallowing, and bolus formation. Saliva is mainly produced by three pairs of major glands: parotid, submandibular, and sublingual glands. To evaluate the effect of each salivary gland on taste preference, we conducted a 48 h two-bottle preference test using mouse models in which the parotid glands (PG), submandibular glands (SMG), or sublingual glands (SLG) were surgically removed. The taste preferences for the five basic tastes of the PG- and SLG-removed mice were similar to those of the control mice. However, in SMG-removed mice, the avoidance of bitter compounds was significantly decreased. These findings indicate that the SMG plays an important role in bitter taste perception among the three major salivary glands. To investigate the reasons for this preference change, we examined the impact of salivary gland removal on the expression of taste-related molecules in the taste buds. No apparent changes were observed in the expression of these molecules after salivary gland removal. When comparing the protein concentration and composition of saliva between the control and salivary gland removal groups, we found that, although the protein concentration did not change significantly, its composition was substantially altered by SMG removal. These results suggest that changes in protein composition in saliva may be one of the factors responsible for the altered bitter preferences observed in the SMG-removed mice.

While activation of autophagy is vital for cellular survival during exposure to ambient heat and exercise, it remains unclear if autophagic activity differs between these heat stress conditions and if aging mediates this response. Young (n=10, mean [SD]: 22 [2] years) and older males (n=10, 70 [5] years) performed 30 min of semi-recumbent cycling (70% maximal oxygen uptake). On a separate day, participants were immersed in warm water for 30 min, with the water temperature adjusted to induce the same increase in core temperature (rectal) as the prior exercise bout. Proteins associated with autophagy, inflammation, apoptosis, and the heat shock response (HSR) were assessed in peripheral blood mononuclear cells via Western blot before and after each exposure and during a 6-hour seated recovery in a temperate environment (∼22°C). No differences in core temperature occurred at end-exposure to exercise or passive heating in either group (both, p≥0.999). Older adults exhibited greater autophagic regulation (significant LC3-II accumulation) to exercise when compared to passive heating at all timepoints (all, p≤0.022). However, passive heating alone may have impaired autophagy (elevated p62; p=0.044). Pro-inflammatory IL-6 was elevated during both conditions (p<0.001) in older adults. Conversely, greater autophagic initiation (i.e., beclin-2) occurred in young adults at end-exercise and 3h recovery when compared to passive heating (both, p≤0.024). The HSR and apoptotic responses were similar between conditions in both groups. While brief exercise stimulates autophagy, exposure to ambient heat stress of an equivalent heat load may underlie autophagic dysregulation in older adults.