Oral saline consumption and pressor responses to acute physical stress.

Sodium induced volume loading may alter pressor responses to physical stress, an early symptom of cardiovascular disease. PURPOSE: Study 1: Determine the time point where total blood volume and serum sodium were elevated following saline consumption. Study 2: Examine the BP response to isometric handgrip (HG) and the cold pressor test (CPT) following saline consumption. METHODS: Study 1: Eight participants drank 423 mL of normal saline (sodium 154 mmol/L) and had blood draws every 30 min for 3 h. Study 2: Sixteen participants underwent two randomized data collection visits; a control and experimental visit 90 min following saline consumption. Participants underwent 2 min of isometric HG, post exercise ischemia (PEI), and CPT. RESULTS: Study 1: Total blood volume (3.8 ± 3.0 Δ%) and serum sodium (3.5 ± 3.6 Δ%) were elevated (P < 0.05) by the 90 min time point. Study 2: There were no differences in mean arterial pressure (MAP) during HG (EXP: 17.4 ± 8.2 ΔmmHg; CON: 19.1 ± 6.0 ΔmmHg), PEI (EXP: 16.9 ± 11.7 ΔmmHg; CON: 16.9 ± 7.8 ΔmmHg), or the CPT (EXP: 20.3 ± 10.8 ΔmmHg; CON: 20.9 ± 11.7 ΔmmHg) between conditions (P > 0.05). MAP recovery from the CPT was slower following saline consumption (1 min recovery: EXP; 15.7 ± 7.9 ΔmmHg, CON; 12.3 ± 8.9 ΔmmHg, P < 0.05). CONCLUSION: Data showed no difference in cardiovascular responses during HG or the CPT between conditions. BP recovery was delayed by saline consumption following the CPT.

Incorporating sprouted chickpea flour in pasta increases brachial artery flow-mediated dilation.

PURPOSE: Consumption of alternative flours, such as sprouted chickpea flour, has shown increased popularity in recent years. Foods rich in antioxidants have been shown to influence brachial artery flow-mediated dilation (FMD), a non-invasive test of a crucial layer of the artery called the endothelium. Partially replacing the semolina flour in pasta with sprouted chickpea flour (SCF) may acutely affect endothelial function post-digestion. We sought to determine if FMD was higher, lower, or the same post-digestion of pasta made with 60% semolina flour and 40% SCF (SCF40) vs. post-digestion of pasta made with 100% semolina flour (SEM100, i.e., control). METHODS: Trolox equivalent antioxidant capacity (TEAC) analysis was performed on the same flour samples. Healthy participants underwent a screening visit and two randomized controlled meal data collection visits (SCF40 and SEM100). At each data collection visit, participants consumed 255 g of pasta with butter. FMD was assessed 2-3 h after pasta consumption. RESULTS: TEAC results showed that SCF40 (2.031 ± 0.096 mmol trolox/100 g sample) had significantly greater antioxidant capacity than SEM100 (1.736 ± 0.046 mmol trolox/100 g sample; p = 0.02). Twenty-two healthy participants (5 men and 17 women; 26 ± 2 years, 66.6 ± 2.3 kg, BMI = 24 ± 1 kg/m2, SBP = 114 ± 3 mmHg, DBP = 75 ± 2 mmHg, HR = 74 ± 3 BPM) were studied. FMD in the SCF40 condition (10.3% ± 1.2%) was greater than the SEM100 condition (7.9% ± 0.8%, p = 0.02). CONCLUSION: These data suggest that partial substitution with sprouted chickpea flour in place of semolina flour in pasta acutely improves post-digestion FMD, which may be beneficial for cardiovascular health (ClinicalTrials.gov Identifier: NCT03801486).

Dietary sodium and nocturnal blood pressure dipping in normotensive men and women.

Impaired nocturnal blood pressure (BP) dipping (i.e., <10% decline in nocturnal BP) is associated with an increased risk of cerebrovascular and cardiovascular diseases. Excess sodium has been shown to impair BP regulation and increase cardiovascular disease risk, yet few studies have assessed the influence of dietary sodium on nocturnal dipping in normotensive adults. The purpose of this study was to determine the effects of dietary sodium on BP dipping in normotensive men and women. Eighty healthy normotensive adults participated in a controlled feeding study (men: n=39, 34±2 years; women: n=41, 41±2 years). Participants consumed a standardized run-in 100 mmol sodium per day diet for 7 days, followed by 7 days of low-sodium (LS; 20 mmol per day) and high-sodium (HS; 300 mmol per day) diets in random order. On the final day of each diet, subjects wore a 24 h ambulatory BP monitor, collected a 24 h urine sample and provided a blood sample. During the run-in diet, 24 h urinary sodium excretion was 79.4±5.1 mmol per 24 h in men and 85.3±5.5 mmol per 24 h in women (P>0.05). Systolic BP dipping was not different between men (11.4±1.0%) and women (11.2±0.9%); (P>0.05). During the HS diet, 24 h urinary sodium excretion increased compared with the LS diet in men (LS=31.7±4.6 mmol per 24 h vs HS=235.0±13.9 mmol per 24 h, P<0.01) and women (LS=25.8±2.2 mmol per 24 h vs HS=234.7±13.8 mmol per 24 h, P<0.01). Despite this large increase in sodium intake and excretion, systolic BP dipping was not blunted in men (LS=8.9±1.0% vs HS=9.4±1.2%, P>0.05) or women (LS=10.3±0.8% vs HS=10.5±0.8%, P>0.05). Among normotensive men and women, HS does not blunt nocturnal BP dipping.

Salt loading has a more deleterious effect on flow-mediated dilation in salt-resistant men than women.

BACKGROUND AND AIMS: Dietary sodium loading has been shown to adversely impact endothelial function independently of blood pressure (BP). However, it is unknown whether dietary sodium loading impacts endothelial function differently in men as compared to women. The aim of this study was to test the hypothesis that endothelial-dependent dilation (EDD) would be lower in men as compared to women in response to a high sodium diet. METHODS AND RESULTS: Thirty subjects (14F, 31±2y; 16M, 29±2y) underwent a randomized, crossover, controlled diet study consisting of 7 days of low sodium (LS; 20 mmol/day) and 7 days of high sodium (HS; 300-350 mmol/day). Salt-resistance was determined by a change in 24-hr mean arterial pressure (MAP) ≤ 5 mm Hg between HS and LS as assessed on day 7 of each diet. Blood and 24-hr urine were also collected and EDD was assessed by brachial artery flow-mediated dilation (FMD). By design, MAP was not different between LS and HS conditions and urinary sodium excretion increased on HS diet (P < 0.01). FMD did not differ between men and women on the LS diet (10.2 ± 0.65 vs. 10.7 ± 0.83; P > 0.05) and declined in both men and women on HS (P < 0.001). However, FMD was lower in men as compared to women on HS (5.7 ± 0.5 vs. 8.6 ± 0.86; P < 0.01). CONCLUSIONS: HS reduced FMD in both men and women. In response to an HS diet, FMD was lower in men compared to women suggesting a greater sensitivity of the vasculature to high sodium in men.

Characterization and localization of a putative oxytocin receptor in the cervix of the oestrous ewe.

The purpose of the present study was to investigate the presence of high-affinity oxytocin-binding sites (putative oxytocin receptors) in the cervix of the non-pregnant ewe. [3H]Oxytocin binding to the peripheral layers of cervical tissue (comprising the serosal layer and the least dense collagenous and muscular layers) and the remaining dense collagenous cervical tissue were studied separately. [3H]Oxytocin-binding sites were detected in membrane fractions prepared from both of these regions, but binding to the peripheral cervix was variable and binding site concentrations were low, hence these were not characterized further. A high-affinity oxytocin-binding site, having a dissociation constant of 1.8 nmol/l, was characterized in the dense collagenous regions of the cervix of ewes killed during the oestrous period. Similar dissociation constants were determined for [Arg8]-vasopressin and the oxytocin-specific agonist [Thr4, Gly7]-oxytocin in competition studies. [3H]Oxytocin binding to peripheral cervical tissue and to the dense collagenous cervix was generally low or undetectable during the luteal phase, but increased in both tissues around the time of luteolysis. Although specific binding to both tissues was variable during the oestrous period, it was higher at this time than during the luteal phase. [3H]Oxytocin-binding site concentrations were also found to be higher within the inner dense collagenous cervix of oestrous ewes than of pregnant, ovariectomized or anoestrous animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Actions of oxytocin and vasopressin on oestrogen-induced electromyographic activity recorded from the uterus and oviduct of anoestrous ewes.

Oxytocin and the related peptide [Arg8]vasopressin (AVP) have previously been shown to bind with equally high affinity to oxytocin binding-sites (presumed oxytocin receptors) present within the uterus and oviduct of oestrous ewes. There is a possibility, therefore, that AVP mediates oxytocic actions through these binding sites. For the present study, ewes in seasonal anoestrus were treated with oestradiol-17 beta (50 micrograms subcutaneously, daily for 2-4 days). It was shown initially that this treatment stimulated the development of high-affinity oxytocin binding-sites (Kd 4.4 +/- 0.8 nmol L-1) which had similar affinity for AVP (Kd 4.2 +/- 0.9 nmol L-1) in the myometrium. The efficacy of oxytocin and AVP in vivo were compared by recording electromyographic (EMG) activity from the ampullary-isthmic junction of the left oviduct and the left uterine horn of four conscious ewes. Before oestradiol treatment there was no EMG response to oxytocin even at supraphysiological (1000 mU) doses. During oestradiol treatment, EMG activity was consistently increased in response to injections of 25 mU and 100 mU oxytocin via the jugular vein, but not to saline or 100 mU AVP. Higher doses of AVP were not investigated because of the possibility of cardiovascular side effects. A subsequent blood sampling experiment showed that maximal concentrations of oxytocin and AVP (achieved in peripheral plasma during the first 2 min following injection into the jugular vein) were of a similar order of magnitude after injection of equivalent doses of the two peptides. It is concluded that AVP probably does not mediate biological activity through the oxytocin receptor in non-pregnant ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of pregnancy and systemic or intrauterine oxytocin infusion on the distribution of endometrial oxytocin receptors in the ewe: an autoradiographic study.

Previous autoradiographic studies have suggested that the regulation of oxytocin receptors differs between endometrial cell types during the ovine oestrous cycle, and that those present on luminal epithelial cells are of particular importance to the regulation of prostaglandin F2 alpha release during luteal regression. The present autoradiographic study compares the distribution of the endometrial oxytocin receptor in day-15 non-pregnant and pregnant ewes. The distribution of the endometrial oxytocin receptor in day-15 non-pregnant ewes infused with systemic or intrauterine oxytocin has also been investigated. Continuous, s.c. infusion of oxytocin (150 mmol/24 h) into ewes (n = 6) between days 10 and 15 of the oestrous cycle significantly increased plasma oxytocin concentrations (to approximately 100 pmol/l). There was no similar increase in systemic oxytocin concentrations in ewes receiving intrauterine (i.u.) oxytocin infusions (10 nmol/24 h) between days 10 and 15 of the oestrous cycle (n = 6). Luteolysis was inhibited in all six animals infused with oxytocin (s.c.) and endometrial oxytocin receptor concentrations were significantly lower on day 15 in these animals (12.8 +/- 6.5 (S.E.M.) fmol/mg protein; P < 0.001) and in pregnant ewes (18.4 +/- 15.4 fmol/mg protein; P < 0.001; n = 8) than in ewes infused with saline (248.6 +/- 67.1 fmol/mg protein; n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of oxytocin infusion on secretion of progesterone and luteinizing hormone and the concentration of uterine oxytocin receptors during the periovulatory period in cloprostenol-treated ewes.

Oxytocin infusions were initiated on day 10 of the oestrous cycle in ewes, and luteal regression was induced by injection of 100 micrograms cloprostenol on day 12. Blood samples were collected at frequent intervals via an indwelling jugular vein cannula to measure concentrations of progesterone and luteinizing hormone (LH) during the luteal and follicular phases in saline (n = 6) and oxytocin (n = 5) infused animals. The oxytocin infusion maintained peripheral plasma concentrations of 53 +/- 3.2 pg oxytocin ml-1 (mean +/- SEM) compared with values of about 1 pg ml-1 during oestrus in control ewes. Oxytocin infusion had no effect on luteal phase progesterone concentrations, the timing of luteolysis, basal luteinizing hormone (LH) secretion, LH pulse frequency, or the timing or height of the LH surge. Treated ewes came into oestrus significantly earlier than controls (P < 0.05) but ovulated normally. Uterine samples collected 96 h after cloprostenol injection (approximately day 2 of the cycle) showed that oxytocin receptor concentrations were significantly higher in the endometrium in ewes that had been given a 5 day oxytocin infusion than in control animals (556 and 262 fmol mg-1 protein, respectively: geometric means from ANOVA, P < 0.001), whereas myometrial receptor concentrations were not affected (113 and 162 fmol mg-1 protein, respectively). We conclude that the previously reported delay in luteal development caused by oxytocin infusion (Wathes et al., 1991) is not due to the inhibition or delay of ovulation, but must instead occur via a direct influence on the developing corpus luteum.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of plasma vasopressin and oxytocin concentrations during the oestrous cycle of the ewe.

Blood samples were collected twice daily (09.30 and 17.00 h) via indwelling jugular-vein cannulae from five ewes throughout an entire oestrous cycle. Additional frequent samples were taken at 30-min intervals for 8 h on each of days 3 (early luteal phase), 9 (midluteal phase), 12 (late luteal phase) and 0 (day of oestrus). Plasma concentrations of arginine vasopressin and oxytocin were measured in all samples by radioimmunoassay and progesterone was measured in the twice-daily samples only. Both oxytocin and progesterone showed the expected pattern of plasma concentrations, increasing during the early luteal phase, reaching a plateau and declining either preceding (oxytocin) or at (progesterone) luteolysis. Vasopressin concentrations showed a significant dependence on the day of cycle (P less than 0.05, analysis of variance) with concentrations lowest at oestrus and minor peaks on days 4 and 8-9. There was no correlation between the concentrations of vasopressin and progesterone. Vasopressin values were significantly higher in the morning than in the afternoon samples (1.3 cf. 0.9 pmol/l; P less than 0.001). Analysis of the frequent samples showed a significant (P less than 0.001) dependence on the time of day for vasopressin but not oxytocin. Values were high throughout the morning, declined to a trough at 15.00 h and rose again by 17.00 h. We conclude that there is a minor variation in the vasopressin concentration during the oestrous cycle, which is not related to the circulating progesterone concentration but could be regulated by oestradiol. We also provide evidence for a diurnal rhythm in the release of vasopressin into the plasma in the ewe.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiographic localization of oxytocin receptors in the endometrium during the oestrous cycle of the ewe.

The present study was designed to determine the localization of the endometrial oxytocin receptor during the ovine oestrous cycle, particularly on day 14, the time of initiation of luteal regression in the ewe. Samples were obtained from 29 ewes at different stages of the oestrous cycle (several during the luteal phase and on every day between day 14 (-2) and day +3 of the oestrous period). Oxytocin receptors were localized autoradiographically in sections of uterine tissue, using the 125I-labelled oxytocin receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid), 2-(ortho-methyl)-Tyr2,Thr4,Orn8, Tyr9-NH2]-vasotocin (125I-labelled OTA). There was some variation in the pattern of 125I-labelled OTA labeling between different uterine tissue samples from the same ewe and also between samples obtained from different ewes thought to be at the same stage of the oestrous cycle. A clear overall pattern did, however, emerge with 125I-labelled OTA-binding sites distributed between luminal epithelial cells, glandular epithelial cells and caruncular stromal cells to varying extents on different days of the cycle. During the luteal phase (days 5-12) clear specific labelling of endometrial tissue was generally absent. On day 14 labelling was evident on the luminal epithelium, but only in nine tissue samples out of a total of 18 studied, indicating that the entire luminal surface did not contain oxytocin receptors at this time. Between the day before oestrus and day 3 of the oestrous cycle the luminal epithelium was consistently labelled.(ABSTRACT TRUNCATED AT 250 WORDS)