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      Oral Contraceptives and Renal Water Handling : A diurnal study in young women

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          Abstract

          To test the hypothesis that use of oral contraceptives ( OC) changes diurnal variation in fluid balance mechanisms including blood pressure, secretion of vasopressin and oxytocin, and renal water and electrolyte excretion. Fifteen naturally cycling ( NC) women in mid‐follicular phase and 11 long‐term OC users were included in a 24‐h standardized inpatient study for measurements of vasopressin, oxytocin, sodium, and osmolality in plasma as well as urinary excretion of electrolytes, aquaporin‐2, and prostaglandin E2. Blood pressure and heart rate were monitored noninvasively. Plasma vasopressin showed circadian rhythm ( P = 0.02) and were similar in both groups ( P = 0.18) including nighttime increases ( P < 0.001). There was no circadian rhythm in plasma oxytocin within ( P = 0.84) or between groups ( P = 0.22). OC users had significantly lower plasma osmolality (Δosm: 3.05 ± 0.29 mosm/kg, P = 0.04) and lower plasma sodium (ΔNa +: 0.91 ± 0.09 mmol/l, P = 0.05). The two groups showed similar nighttime decreases in diuresis (1.08 ± 0.04 mL/(kg·h), P < 0.001) and increases in urine osmolality (109 ± 9 mosm/kg, P = 0.02), but similar rates of excretion of Aquaporin‐2, prostaglandin E2 and sodium. Nighttime decreases in mean arterial pressure of approximately 13% were significant in both groups ( P < 0.001), but 24‐h average mean arterial pressure was significantly higher in OC users than in controls (+4.7 ± 0.4 mmHg, P = 0.02). Packed cell volumes were similar between groups ( P = 0.54). OC does not change the diurnal patterns of renal fluid excretion, but resets the osmoreceptors for vasopressin release and leads to a significant increase in arterial blood pressure.

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          Activation of the prostaglandin system in response to sleep loss in healthy humans: potential mediator of increased spontaneous pain.

          Insufficient duration of sleep is a highly prevalent behavioral pattern in society that has been shown to cause an increase in spontaneous pain and sensitivity to noxious stimuli. Prostaglandins (PGs), in particular PGE2, are key mediators of inflammation and pain, and we investigated whether PGE2 is a potential mediator in sleep-loss-induced changes in nociceptive processing. Twenty-four participants (7 females, age 35.1+/-7.1 years) stayed for 7 days in the Clinical Research Center. After two baseline days, participants were randomly assigned to either 3 days of 88 h of sleep deprivation (TSD, N=15) or 8h of sleep per night (N=9), followed by a night of recovery sleep. Participants rated the intensity of various pain-related symptoms every 2h across waking periods on computerized visual analog scales. PGE2 was measured in 24-h-urine collections during baseline and third sleep deprivation day. Spontaneous pain, including headache, muscle pain, stomach pain, generalized body pain, and physical discomfort significantly increased by 5-14 units on a 100-unit scale during TSD, compared to the sleep condition. Urinary PGE2 metabolite significantly increased by about 30% in TSD over sleep condition. TSD-induced increase in spontaneous pain, in particular headache and muscle pain, was significantly correlated with increase in PGE2 metabolite. Activation of the PGE2 system appears to be a potential mediator of increased spontaneous pain in response to insufficient sleep.
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            Effects of oral contraceptives on body fluid regulation.

            To test the hypothesis that estrogen reduces the operating point for osmoregulation of arginine vasopressin (AVP), thirst, and body water balance, we studied nine women (25 +/- 1 yr) during 150 min of dehydrating exercise followed by 180 min of ad libitum rehydration. Subjects were tested six different times, during the early-follicular (twice) and midluteal (twice) menstrual phases and after 4 wk of combined [estradiol-norethindrone (progestin), OC E + P] and 4 wk of norethindrone (progestin only, OC P) oral contraceptive administration, in a randomized crossover design. Basal plasma osmolality (P(osm)) was lower in the luteal phase (281 +/- 1 mosmol/kgH(2)O, combined means, P < 0.05), OC E + P (281 +/- 1 mosmol/kgH(2)O, P < 0.05), and OC P (282 +/- 1 mosmol/kgH(2)O, P < 0. 05) than in the follicular phase (286 +/- 1 mosmol/kgH(2)O, combined means). High plasma estradiol concentration lowered the P(osm) threshold for AVP release during the luteal phase and during OC E + P [x-intercepts, 282 +/- 2, 278 +/- 2, 276 +/- 2, and 280 +/- 2 mosmol/kgH(2)O, for follicular, luteal (combined means), OC E + P, and OC P, respectively; P < 0.05, luteal phase and OC E + P vs. follicular phase] during exercise dehydration, and 17beta-estradiol administration lowered the P(osm) threshold for thirst stimulation [x-intercepts, 280 +/- 2, 279 +/- 2, 276 +/- 2, and 280 +/- 2 mosmol/kgH(2)O for follicular, luteal, OC E + P, and OC P, respectively; P < 0.05, OC E + P vs. follicular phase], without affecting body fluid balance. When plasma 17beta-estradiol concentration was high, P(osm) was low throughout rest, exercise, and rehydration, but plasma arginine vasopressin concentration, thirst, and body fluid retention were unchanged, indicating a lowering of the osmotic operating point for body fluid regulation.
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              Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney.

              Vasopressin (antidiuretic hormone) regulates body water balance by controlling water permeability of the renal collecting ducts. The control mechanisms may involve alterations in the number or unit conductance of water channels in the apical plasma membrane of collecting-duct cells. How this occurs is unknown, but indirect evidence exists for the "shuttle" hypothesis, which states that vasopressin causes exocytic insertion of water channel-laden vesicles from the apical cytosol. To test key aspects of the shuttle hypothesis, we have prepared polyclonal antisera against the recently cloned collecting-duct water channel protein and used the antisera in immunolocalization studies (light and electron microscopic levels) in thin and ultrathin cryosections from rat kidney. Labeling was seen exclusively in collecting-duct principal cells and inner medullary collecting-duct cells. Apical membrane labeling was intense. There was heavy labeling of abundant small subapical vesicles and of membrane structures within multivesicular bodies. In addition, labeling of basolateral plasma membranes in inner medullary collecting ducts was present. Depriving rats of water for 24 or 48 hr markedly increased collecting-duct water-channel protein expression determined by immunoblotting and immunolabeling. These results are compatible with at least two complementary modes of water-channel regulation in collecting-duct cells: (i) control of channel distribution between the apical membrane and a reservoir in subapical vesicles (shuttle hypothesis) and (ii) regulation of the absolute level of expression of water-channel protein.
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                Author and article information

                Contributors
                graugaard@ki.au.dk
                Journal
                Physiol Rep
                Physiol Rep
                10.1002/(ISSN)2051-817X
                PHY2
                physreports
                Physiological Reports
                John Wiley and Sons Inc. (Hoboken )
                2051-817X
                12 December 2017
                December 2017
                : 5
                : 23 ( doiID: 10.1002/phy2.2017.5.issue-23 )
                : e13547
                Affiliations
                [ 1 ] Department of Urology University Hospital of Aarhus Aarhus N Denmark
                [ 2 ] Department of Clinical Physiology and Nuclear Medicine University Hospital of Aarhus Aarhus N Denmark
                [ 3 ] Institute of Molecular Medicine University of Southern Denmark Odense Denmark
                [ 4 ] Institute of Clinical Medicine University Hospital of Aarhus Aarhus N Denmark
                Author notes
                [*] [* ] Correspondence

                Charlotte Graugaard‐Jensen, Department of Urology, Aarhus University Hospital, Palle Juul‐Jensens Boulevard 99, Aarhus N, Denmark.

                Tel: + 45 30915671

                Fax: +45 78452718

                E‐mail: graugaard@ 123456ki.au.dk

                Article
                PHY213547
                10.14814/phy2.13547
                5727291
                56efff3d-ff7b-4a61-9f3d-6c9482b0ee10
                © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 November 2017
                : 17 November 2017
                : 21 November 2017
                Page count
                Figures: 4, Tables: 1, Pages: 9, Words: 5701
                Categories
                Renal Filtration
                Blood Pressure
                Reproductive Conditions, Disorders and Treatments
                Original Research
                Original Research
                Custom metadata
                2.0
                phy213547
                December 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.8 mode:remove_FC converted:13.12.2017

                arginine vasopressin,diuresis,diurnal rhythm,oral contraceptives,oxytocin,prostaglandin e2

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