Antidiuretic hormone (ADH) is a fundamental regulator of fluid and electrolyte homeostasis. Osmotically unregulated ADH secretion during intravenous fluid therapy has been implicated in the development of iatrogenic hyponatraemia. The case report and 3 prospective studies of this thesis provide evidence for this and examine the relative contributions of salinity versus infusion rate of intravenous fluids to the development of hyponatraemia. Two studies of plasma and urinary electrolytes and osmolality during intravenous rehydration of children with gastroenteritis were performed. The first, an observational study of 52 children receiving 0.45% (N/2) saline documented persistently raised plasma ADH concentrations independent of plasma sodium. In both studies, plasma and urinary biochemistry suggested osmotically unregulated ADH action. When N/2 and NS were compared in a randomised study of 102 children, NS emerged as superior in the prevention and correction of hyponatraemia, independent of infusion rate. In the third study, 124 pre-operative children were randomised to receive N/2 or NS intravenously at 100% or 50% of maintenance rates post-operatively. Plasma ADH concentrations increased in all groups, and the plasma and urinary biochemistry indicated persistent non-osmotic ADH activity in some children for up to 24 hours. Baseline urinary tonicity approximated NS. Comparison of urinary tonicity with the infused fluid largely explained changes observed in plasma sodium. The risk of hyponatraemia was decreased by isotonic saline but not fluid restriction; however plasma sodium concentration decreased in the NS 100% group between 8 and 24 hours, suggesting that a decreased rate should be considered during prolonged intravenous fluid administration. Fourteen (23%; 7NS) of those on 50% maintenance were assessed as dehydrated, with hypernatraemia in 3 receiving NS50%. The chloride load associated with NS in the second and third studies was not associated with the development of acidosis. The studies also showed that 2.5% dextrose resolved and prevented hypoglycaemia in children with gastroenteritis but was inadequate to prevent hypoglycaemia and/or ketosis in 38% of children under 6 years when infused at maintenance rates. Non-osmotically regulated ADH activity in hospitalised children is common, in the face of which, isotonic is superior to hypotonic saline in decreasing the risk of hyponatraemia.

Preeclampsia is a devastating disorder of pregnancy characterized by high blood pressure, proteinuria, headache, renal glomerular endotheliosis, multi-organ system failure, and fetal and maternal demise. As reviewed in Chapter I, not much is known about the pathogenesis of preeclampsia, contributing to a lack of biomarkers and treatments for the disease. In Chapter II, we review arginine vasopressin, a circulating neuropeptide hormone with important fluid balance and cardiovascular actions. Vasopressin binds to numerous receptors throughout the body to elicit its effects and is associated with various disease states. In Chapter III, we discuss evidence for vasopressin as an etiology of preeclampsia. Specifically, that vasopressin secretion is elevated very early in pregnancies affected by preeclampsia and infusion of vasopressin into pregnant C57BL/6J mice causes physiological features similar to those seen in preeclampsia. In Chapter IV, we show that vasopressin administration during mouse pregnancy models specific subtypes of preeclampsia through time- and receptor-specific mechanisms. The role of angiotensin 1a receptors on vasopressin-producing cells in fluid homeostasis is shown in Chapter V and their role in metabolism is depicted in Chapter VI. Overall, we conclude that vasopressin is an important mediator of features of preeclampsia and that angiotensin 1a receptors on vasopressin-producing cells are important for normal fluid homeostasis.

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The ovary undergoes cyclic changes in follicular growth and luteogenesis due to the action of gonadotropins and steroids. The ovary and especially the corpus luteum has an exteremely high blood flow. There is a gap in our knowledge about the physiological role of the high blood flow of the corpus luteum. The production of lactate, progesterone and cyclic AMP of follicles and corpora lutea incubated in vitro was analyzed and related to the tissue content of ATP to elucidate possible connections between oxygen and substrate levels and energy consumption, steroid output and LH responsiveness in vitro. It was also considered of interest to investigate if the oxygen tensions needed for ATP and progesterone production of the follicle and the corpus luteum differed. A corpus luteum model using adult pseudopregnant rats was developed and characterized according to criteria for identification of corpora lutea as well as levels of plasma steroids and gonadotropins. In vitro progesterone production was compared to plasma progesterone levels. The absolute blood flow of corpora lutea of different ages and the response to injection of hCG, noradrenaline and antidiuretic hormone was investigated with the microsphere technique. Relative blood flow changes of follicles and corpora lutea during follicular growth and luteogenesis in vivo were studied by injecting radiolabelled microspheres to anaesthetized immature rats at different time periods after injection of an ovulatory dose of pregnant mare serum gonadotropin. This approach was chosen to investigate the possible relation between follicular/luteal blood flow, steroid output and morphology in relation to the endogenous gonadotropin surge, ovulation and luteogenesis. Hormonal stimulation by injection of hCG and noradrenaline increased total ovarian blood flow but no evidence was found for a parallelism between luteotropism and blood flow. The increasing effect of hCG on ovarian blood flow was partly due to a shunting of blood from the uterus towards the ovary. The antidiuretic hormone potently decreased ovarian and uterine blood flow by 80-90% while blood flow of some other organs (e.g. kidney and spleen) were hardly affected. The corpus luteum of pseudopregnancy was found to produce 15“ 20 times more progesterone in vitro as compared to the preovulatory follicle. The steroidogenesis and energy production of corpora lutea was found to be more sensitive to decreases in oxygen tension in terms of tissue ATP levels and LH responsiveness of progesterone production while the follicle could compensate by increasing glycolysis. A parallelism between follicular/luteal blood flow and progesterone production in vivo was found. It was shown that the formation, growth and progesterone production of the corpus luteum was accompanied by an increase in blood flow as well as vascularization as seen under the light microscope. The endogenous gonadotropin surge did not change follicular blood flow due to the development of a follicular oedema. We hypothesize that the corpus luteum function in vivo and in vitro is dependent on higher energy levels than the preovulatory follicle and that the transformation of the follicle to a corpus luteum is supported by a high nutritive blood flow possibly to support a high demand for energy-rich substrates. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1987, härtill 7 uppsatser.</p> / digitalisering@umu