Role of Mineralocorticoids in the Natriuresis of Water Immersion in Man

The role of aldosterone suppression in mediating the natriuresis of water immersion was assessed in six normal male subjects. All subjects were studied on four occasions while they were in balance on a diet containing 150 mEq of sodium and 100 mEq of potassium daily: during a control period, following deoxycorticosterone acetate (DOCA) treatment for 24 hours (Cont + DOCA), during water immersion to the neck (immersion), and during water immersion following DOCA treatment (Imm + DOCA). Immersion resulted in highly significant increases in the rates of sodium and potassium excretion compared with control beginning in the first hour. Although treatment with DOCA decreased the natriuresis of immersion ( P < 0.01), the rate of sodium excretion was still three- to fourfold greater during Imm + DOCA than it was during the comparable Cont + DOCA periods ( P < 0.01). Cessation of water immersion resulted in a marked decrease in urine flow and free water clearance occurring within the initial 30 minutes of recovery ( P < 0.005). Although the rate of sodium excretion also decreased following cessation of immersion, it continued to exceed both preimmersion values ( P < 0.01) and the comparable control values throughout the recovery hour ( P < 0.01). These observations suggest that the natriuresis of immersion cannot be completely accounted for by immersion-induced suppression of aldosterone. The continuing natriuresis occurring despite the progressive volume contraction induced by immersion suggests that the natriuretic stimulus is sufficiently potent to override the compensatory mechanisms which are known to participate in defense of volume homeostasis. Furthermore, the delay in the disappearance of the natriuresis suggests that a humoral factor rather than more rapidly acting hemodynamic and neural mechanisms may mediate the natriuresis

Comparison of diphenhydramine and modafinil on arousal and autonomic functions in healthy volunteers

Arousal is regulated by the interplay between wakefulness- and sleep-promoting nuclei. Major wakefulness-promoting nuclei are the histaminergic tuberomamillary nucleus (TMN) of the hypothalamus and the noradrenergic locus coeruleus (LC) of the pons, which also play a role in autonomic regulation. First generation antihistamines, such as diphenhydramine, are likely to cause sedation by blocking excitatory H1 histamine receptors in the cerebral cortex, and the anti-narcolepsy drug modafinil may promote wakefulness by activating the locus coeruleus. We compared the effects of single doses of diphenhydramine (75 mg) and modafinil (200 mg) on arousal and autonomic functions in 16 healthy male volunteers, using a placebo-controlled, balanced, double-blind design. Arousal was assessed by critical flicker fusion frequency (CFFF), visual analogue scales (VAS) and pupillary fatigue waves (Pupillographic Sleepiness Test (PST)). Autonomic functions measured included resting pupil diameter, light and darkness reflex responses, blood pressure, heart rate and salivation. Data were analysed with ANOVA, with multiple comparisons. Diphenhydramine had sedative effects as shown by reductions in CFFF, VAS alertness ratings and increases of the indices of pupillary fatigue. Modafinil had alerting effects as indicated by reductions in the measures of pupillary fatigue. Comparison of pre-post medication changes in pupil diameter showed a decrease after diphenhydramine and an increase after modafinil. Diphenhydramine reduced salivation, and modafinil increased systolic blood pressure. In conclusion, diphenhydramine and modafinil evoked opposite effects on arousal and sympathetic functions, which are likely to reflect their interaction with the central histaminergic and noradrenergic systems. Hyposalivation by diphenhydramine is likely to be due to its additional anticholinergic property