Endocrine and ingestive behavioral responses to fluid deprivation in sheep chronically exposed to ethanol.

Endocrine responses to fluid deprivation/restoration and preference for ethanol solution vs. water were assessed in sheep maintained for 5 months on a 10% ethanol solution as their sole source of fluid. Blood pressure, body weight, plasma composition and hormone levels of the alcohol maintained sheep were all within a normal range, except for high plasma concentrations of ANG II and ALDO. During fluid deprivation, AVP concentration increased and fluid-deprived sheep displayed a natriuresis and then a rehydration anti-natriuresis. Sheep did not drink the 10% ethanol solution avidly upon fluid restoration, preferring to drink steadily over the following 24 h; there was an associated increase in blood alcohol concentration (BAC). PRC, ANG II and ALDO all increased throughout the fluid restoration period, whereas plasma AVP and ANP gradually fell. In a separate experiment when water was also supplied to the sheep, they preferred water to 10% ethanol; however, alcohol intake was not eliminated. Overall, this degree of chronic consumption of 10% ethanol solution did not appear to adversely affect physiological mechanisms concerned with body fluid homeostasis after fluid deprivation conditions.

Assessment of airway function in young children with asthma: comparison of spirometry, interrupter technique, and tidal flow by inductance plethsmography.

The assessment of airway function in young children requires adaptation of techniques designed for adults and/or application of techniques that do not require complex respiratory maneuvers. We sought to assess two methods of measuring airway function: time to peak expiratory flows as a ratio of expiratory time (T(PTEF)/T(E)), derived from respiratory inductance plethysmography, and total respiratory resistance by the interrupter technique (Rint), both obtained during quiet tidal breathing. Both techniques were referenced to FEV1 and flow at 50% expired volume (FEF50) from conventional spirometry in 30 children aged 4-8 years (median age, 6.9; range, 4.5-8.5 years) with a physician diagnosis of asthma and who were able to perform FEV1 with a repeatability of at least 8%. T(PTEF)/T(E) and Rint were performed in random order followed by spirometry, in order to reduce the possible effects of pulmonary stretch on tidal breathing measures. Coefficients of variation (CV) and mean absolute change/baseline standard deviation were derived for each measurement. Baseline FEV1 did not correlate significantly with T(PTEF)/T(E) (r = 0.025), but did correlate with Rint (r = 0.737, P < 0.001); respective relationships for change after bronchodilator were r = 0.09 (ns) and r = 0.64 (P < 0.001). FEF50 also correlated significantly with Rint (R = 0.769, P < 0.001) but not with T(PTEF)/T(E). FEV1 and FEF50 both increased postbronchodilator, with respective mean changes of 11.4% and 28% (P < 0.001), while Rint decreased by 24.3% (P < 0.001). No significant changes were noted for T(PTEF)/T(E). T(PTEF)/T(E) derived from inductance plethysmography does not detect mild airway obstruction or modest changes in airway caliber following bronchodilator in young children with asthma. The interrupter technique may have a role in assessing baseline airway function and response to therapy in children unable to perform reliable spirometry, and/or when the investigator wishes to avoid the possible influence of forced maneuvers on airway tone.

The effect of losartan on drinking and NaCl intake in the rat in response to hyperosmotic and hypovolaemic stimuli: effect of route of administration and strain of rat.

Intracerebroventricular 100,000 pmol losartan (an AT1-receptor blocker) inhibited the initial drinking response of Wistar rats to 1 ml 2 M NaCl given subcutaneously but the intake over 3 h was not significantly inhibited. The same dose of the AT2-receptor blocker PD123319 had a more long-lasting inhibitory effect. Rats of three different strain, Wistar, Wistar-Kyoto (WK), and SH (spontaneously hypertensive), were subjected to sodium depletion using frusemide and a low-sodium diet; in the 3 h after 1.8% NaCl was made available, the intakes were 11.6 +/- 1.7 (SEM), 4.1 +/- 1.2 and 12.4 +/- 1.3 ml, respectively; water intakes in the same period averaged 4.2 +/- 1.1, 5.0 +/- 1.1 and 8.3 +/- 1.8 ml. The intake of both fluids by Wistar rats was not significantly affected by either losartan or PD123319. The intake of both saline and water in SHR rats was reduced by losartan. In evaluating the effect of antagonists to angiotensin II on the intake of water and NaCl in response to perturbations of hydromineral balance, difference in the route of administration of the stimulus and strain of the animals used must therefore be taken into account.

The effect of a 72-h fast on plasma levels of pituitary, adrenal, thyroid, pancreatic and gastrointestinal hormones in healthy men and women.

Seventeen human subjects fasted without electrolyte replacement for 3 days and hormone levels were measured before, during and after the fast. Immediate consequences of the fasting state in healthy human subjects include a marked increase in plasma cortisol. ACTH, beta-endorphin, beta-lipotrophic hormone, adrenaline, noradrenaline and dopamine. Levels of all these hormones were much greater on the first morning of the fast than in the post-prandial state, even though the plasma glucose level was no lower than that observed on the morning before the fast began. A clear fall in TSH and tri-iodothyronine (T3) levels was observed, but thyroxine levels did not change significantly. Insulin levels fell whereas proinsulin levels did not fall during the fast, though they did rise markedly upon re-feeding. An increase in GH levels was particularly apparent in male subjects, but was also seen in females when evening samples were compared. Pancreatic glucagon showed a modest rise during the fast, but fell again on refeeding; total glucagon also rose as the fast proceeded, but increased markedly upon re-feeding. Levels of gastrin and peptide YY remained low during the fast. Plasma electrolyte levels were unchanged. The following were closely correlated: cortisol with ACTH, T3 with log10 TSH, dopamine with noradrenaline, and (negatively, during the fast) pancreatic glucagon with glucose.

The site of the dipsogenic action of angiotensin II in the North American opossum.

Adult North American opossums (Didelphis virginiana), predominantly nocturnal water drinkers, were found to respond by drinking to water deprivation, cellular dehydration produced by intravenous infusion of hypertonic saline, and to both intravenous and intracerebroventricular administration of angiotensin II (AII). By taking advantage of the absence of the corpus callosum, an anatomical characteristic of the marsupial, we removed the subfornical organ and implanted a cannula into the anterior third ventricle under direct visual guidance. In these animals: (1) spontaneous drinking, and responses to water deprivation and cellular dehydration were unaffected; (2) after a postoperative period of unresponlsiveness, attenuated and unreliable responses only to high doses of intracerebroventricular AII could be elicited; and (3) the dipsogenic effect of intravenous AII was abolished. We conclude that the subfornical organ is necessary for the physiologically appropriate effect of AII on drinking but that, in the absence of the subfornical organ, the brain can mediate the dipsogenic effect of intracranially administered AII, although the physiological significance of the latter phenomenon is unclear.

Dependence of spontaneous and angiotensin-induced drinking in the rat upon the oestrous cycle and ovarian hormones.

The influence of the oestrous cycle on spontaneous and dipsogen-induced drinking was studied in female rats. Spontaneous fluid intake was lowest on the day of oestrus. Drinking induced by subcutaneous isoprenaline, and by angiotensin II (injected into the preoptic area), also showed marked cyclical variation, being lower at pro-oestrus and oestrus than at other stages of the cycle. Drinking induced by subcutaneous hypertonic NaCl or by intracranial carbachol did not vary with the oestrous cycle. Cyclicity of spontaneous and of angiotensin-induced water intake was not apparent in rats before puberty or after ovariectomy. Ovariectomy reduced drinking in response to isoprenaline. Treatment with oestradiol benzoate (20 micrograms) caused a reduction in spontaneous water intake, but a marked increase in the drinking response to isoprenaline. Treatment with oestradiol benzoate and progesterone (2.5 mg) caused a larger decrease in spontaneous water intake and an insignificant increase in isoprenaline-induced drinking. Water intake induced by subcutaneous hypertonic saline was unaffected by gonadal steroids. The results provide further evidence for the view that the thirst of extracellular origin, in which the renin-angiotensin system is involved, is brought about by mechanisms different from those that respond to cellular dehydration. Only drinking caused by activation of extracellular mechanisms appeared to be sensitive to the ovarian cycle and to ovarian hormones.

The control of parturition.

PIP: A chart showing the principal maternal and fetal mechanisms which may control the onset of parturition is presented. Many factors influence the contractive activity of the uterus. These factors are discussed and include autonomic motor innervation, estrogens, external environment, fetal stress, ACTH and corticosteroids, mechanical stimulation, oxytocin, progesterone, and prostaglandins. Authorities are without agreement as to the relative importance of these factors to the determination of the time of onset of labor. The crucial triggering mechanism could differ between species, between individuals of a species and on successive occasions in the same individual. Some feel 1 particular mechanism is crucial, others support a balance between factors. Parturition is described as a "cascade phenomenon" in which a number of positive feedback mechanisms act together to maintain and carry the process through to completion. The stages of parturition are listed. Molecular structure of crucial steroids are presented. Graphs display the duration of pregnancy according to maternal weight for a variety of species and in a primiparous group of women. Circulating estrogen and progesterone levels in maternal plasma and placental weights during pregnancy in women and sheep are depicted.^ieng

Spontaneous activity of single neurones in the hypothalamus of rabbits during sleep and waking.

1. A method is described for recording from single cells in the hypothalamus of unanaesthetized freely moving rabbits. Behaviour, bodily movement, skin and brain temperatures and e.e.g. were monitored.2. Patterns of unit firing during slow sleep, paradoxical sleep and waking were studied in several regions of the hypothalamus, thalamus and in the septum.3. Of the 144 cells analysed from waking to slow sleep, fifty-six (39%) decreased mean firing rates, thirty (21%) increased spike discharges and fifty-eight (40%) showed no marked change. Dorsal hypothalamic and massa intermedia thalamic cells fired in brief high frequency clusters during slow sleep with a characteristic ;bimodal' interspike interval histogram. Waking and paradoxical sleep abolished these cluster discharges with a concomitant change to an ;asymmetric' histogram.4. Of the thirty-two cells observed during the three states of waking, slow sleep and paradoxical sleep, a majority (twenty-five or 78%) showed their highest rates of spontaneous discharge during paradoxical sleep. Discharge rates of cells sometimes changed in the course of paradoxical sleep according to the presence or absence of phasic events such as myoclonic motor activity. Two hypothalmic cells were almost totally arrested during paradoxical sleep.5. Analysis of unit firing rates during spontaneous rises in brain temperature during waking and paradoxical sleep revealed that a majority of the neurones (22/24) changed their discharge rates in relation to behaviour rather than to brain temperature. Two cells did appear to respond specifically to the central thermal stimulus.6. Hypothalamic cells do not behave as a homogeneous population in relation to changes in the state of arousal of the rabbit. Spontaneous changes in cell discharge related to sleep-waking behaviour must be considered in any interpretation of hypothalamic unit activity as related to neuroendocrine or autonomic mechanisms.