We investigated the biomechanical relationship between intraluminal pressure within small mesenteric resistance arteries, oxidant activation of PKG, Ca2+ sparks, and BK channel vasoregulation. Mesenteric resistance arteries from wild type (WT) and genetically modified mice with PKG resistance to oxidative activation were studied using wire and pressure myography. Ca2+ sparks and Ca2+ transients within vascular smooth muscle cells of intact arteries were characterized using high-speed confocal microscopy of intact arteries. Arteries were studied under conditions of varying intraluminal pressure and oxidation. Intraluminal pressure specifically, rather than the generic stretch of the artery, was necessary to activate the oxidative pathway. We demonstrated a graded step activation profile for the generation of Ca2+ sparks and also a functional "ceiling" for this pressure --sensitive oxidative pathway. During steady state pressure - induced constriction, any additional Ca2+ sensitive-K+ channel functional availability was independent of oxidant activated PKG. There was an increase in the amplitude, but not the Area under the Curve (AUC) of the caffeine-induced Ca2+ transient in pressurized arteries from mice with oxidant-resistant PKG compared with wild type. Overall, we surmise that intraluminal pressure within resistance arteries controls Ca2+ spark vasoregulation through a tightly controlled pathway with a graded onset switch. The pathway, underpinned by oxidant activation of PKG, cannot be further boosted by additional pressure or oxidation once active. We propose that these restrictive characteristics of pressure-induced Ca2+ spark vasoregulation confer stability for the artery in order to provide a constant flow independent of additional pressure fluctuations or exogenous oxidants.
The effects of background noise on speech-evoked cortical auditory evoked potentials (CAEPs) can provide insight into the physiology of the auditory system. The purpose of this study was to determine background noise effects on neural coding of different phonemes within a syllable. CAEPs were recorded from 15 young normal-hearing adults in response to speech signals /s/, /ɑ/, and /sɑ/. Signals were presented at varying signal-to-noise ratios (SNRs). The effects of SNR and context (in isolation or within syllable) were analyzed for both phonemes. For all three stimuli, latencies generally decreased and amplitudes generally increased as SNR improved, and context effects were not present; however, the amplitude of the /ɑ/ response was the exception, showing no SNR effect and a significant context effect. Differential coding of /s/ and /ɑ/ likely result from level and timing differences. Neural refractoriness may result in the lack of a robust SNR effect on amplitude in the syllable context. The stable amplitude across SNRs in response to the vowel in /sɑ/ suggests the combined effects of (1) acoustic characteristics of the syllable and noise at poor SNRs and (2) refractory effects resulting from phoneme timing at good SNRs. Results provide insights into the coding of multiple-onset speech syllables in varying levels of background noise and, together with behavioral measures, may help to improve our understanding of speech-perception-in-noise difficulties.
Excessive sodium (Na+) intake in modern society has been associated with several chronic disorders such as hypertension. Several studies suggest that early life events can program physiological systems and lead to functional changes in adulthood. Therefore, we investigated behavioral and neuroendocrine responses under basal conditions and after 48 h of water deprivation in adult (60-day-old Wistar rats) male, Wistar rats originating from dams were offered only water or 0.15 mol/L NaCl during pregnancy and lactation. Early life salt exposure induced kidney damage, as shown by a higher number of ED-1 positive cells (macrophages/monocytes), increased daily urinary volume and Na+ excretion, blunted basal water intake and plasma oxytocin levels, and increased plasma corticosterone secretion. When challenged with water deprivation, animals exposed to 0.15 mol/L NaCl during early life showed impaired water intake, reduced salt preference ratio, and vasopressin (AVP) secretion. In summary, our data demonstrate that the perinatal exposure to excessive Na+ intake can induce kidney injury in adult offspring and significantly affect the key mechanisms regulating water balance, fluid intake, and AVP release in response to water deprivation. Collectively, these novel results highlight the impact of perinatal programming on the homeostatic mechanisms regulating fluid and electrolyte balance during exposure to an environmental stress (i.e. dehydration) in later life.
This experiment aimed to investigate the efficacy of twice-daily, nonconsecutive heat acclimation (TDHA) in comparison to once-daily heat acclimation (ODHA) and work matched once- or twice-daily temperate exercise (ODTEMP, TDTEMP) for inducing heat adaptations, improved exercise tolerance, and cytokine (immune) responses. Forty males, matched biophysically and for aerobic capacity, were assigned to ODHA, TDHA, ODTEMP, or TDTEMP. Participants completed a cycling-graded exercise test, heat acclimation state test, and a time to task failure (TTTF) at 80% peak power output in temperate (TTTFTEMP : 22°C/40% RH) and hot conditions (TTTFHOT : 38°C/20% RH), before and after 10-sessions (60 min of cycling at ~2 W·kg-1 ) in 45°C/20% RH (ODHA and TDHA) or 22°C/40% RH (ODTEMP or TDTEMP). Plasma IL-6, TNF-α, and cortisol were measured pre- and postsessions 1, 5, and 10. ODHA and TDHA induced equivalent heat adaptations (P 0.05) following ODHA (+14 ± 4%), TDHA (14 ± 8%), ODTEMP (9 ± 10%) or TDTEMP (8 ± 13%). Acute (P 0.05) increases were observed in IL-6, TNF-α, or cortisol during ODHA and TDHA, or ODTEMP and TDTEMP. Once- and twice-daily heat acclimation conferred similar magnitudes of heat adaptation and exercise tolerance improvements, without differentially altering immune function, thus nonconsecutive TDHA provides an effective, logistically flexible method of HA, benefitting individuals preparing for exercise-heat stress.